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https://proteopedia.org/api.php?action=feedcontributions&feedformat=atom&user=Christophe+Zhuge Proteopedia - User contributions [en] 2026-10-05T01:19:59Z User contributions MediaWiki 1.43.8 https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3354836 Sandbox Reserved 1660 2021-02-12T20:22:28Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <StructureSection load='3GMQ' size='350' 'frame'='true' side='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/3'><br /> <br /> =='''Structure of mouse CD1d'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|190px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br><br /> <br /> == Structure ==<br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref>: <br><br /> :- an <scene name='86/868193/Alpha_chain/4'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> :- a <scene name='86/868193/Beta-2-microglobulin_chain/3'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/2'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/2'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Conformational_variations/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="affinity"/><ref name="site"/><ref>McCarthy, C.; Shepherd, D.; Fleire, S.; Stronge, V. S.; Koch, M.; Illarionov, P. A.; Bossi, G.; Salio, M.; Denkberg, G.; Reddington, F.; Tarlton, A.; Reddy, B. G.; Schmidt, R. R.; Reiter, Y.; Griffiths, G. M.; van der Merwe, P. A.; Besra, G. S.; Jones, E. Y.; Batista, F. D.; Cerundolo, V. The Length of Lipids Bound to Human CD1d Molecules Modulates the Affinity of NKT Cell TCR and the Threshold of NKT Cell Activation. J Exp Med 2007, 204 (5), 1131–1144. https://doi.org/10.1084/jem.20062342.</ref>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="affinity"/><ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref name="affinity"/>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> *[[3gmq]]<br /> *[[4f7c]]<br /> <br /> == References ==<br /> {{Reflist}}<br /> <br /> </StructureSection></div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3354835 Sandbox Reserved 1660 2021-02-12T19:33:16Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <StructureSection load='3GMQ' size='350' 'frame'='true' side='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1'><br /> <br /> =='''Structure of mouse CD1d'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|190px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br><br /> <br /> == Structure ==<br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref>: <br><br /> :- an <scene name='86/868193/Alpha_chain/4'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> :- a <scene name='86/868193/Beta-2-microglobulin_chain/3'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/2'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/2'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="affinity"/><ref name="site"/><ref>McCarthy, C.; Shepherd, D.; Fleire, S.; Stronge, V. S.; Koch, M.; Illarionov, P. A.; Bossi, G.; Salio, M.; Denkberg, G.; Reddington, F.; Tarlton, A.; Reddy, B. G.; Schmidt, R. R.; Reiter, Y.; Griffiths, G. M.; van der Merwe, P. A.; Besra, G. S.; Jones, E. Y.; Batista, F. D.; Cerundolo, V. The Length of Lipids Bound to Human CD1d Molecules Modulates the Affinity of NKT Cell TCR and the Threshold of NKT Cell Activation. J Exp Med 2007, 204 (5), 1131–1144. https://doi.org/10.1084/jem.20062342.</ref>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="affinity"/><ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref name="affinity"/>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> *[[3gmq]]<br /> *[[4f7c]]<br /> <br /> == References ==<br /> {{Reflist}}<br /> <br /> </StructureSection></div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3354834 Sandbox Reserved 1660 2021-02-12T19:31:27Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <StructureSection load='3GMQ' size='350' 'frame'='true' side='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1'><br /> <br /> =='''Structure of mouse CD1d'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|190px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br><br /> <br /> == Structure ==<br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref>: <br><br /> :- an <scene name='86/868193/Alpha_chain/4'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> :- a <scene name='86/868193/Beta-2-microglobulin_chain/3'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/2'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/2'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/3'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="affinity"/><ref name="site"/><ref>McCarthy, C.; Shepherd, D.; Fleire, S.; Stronge, V. S.; Koch, M.; Illarionov, P. A.; Bossi, G.; Salio, M.; Denkberg, G.; Reddington, F.; Tarlton, A.; Reddy, B. G.; Schmidt, R. R.; Reiter, Y.; Griffiths, G. M.; van der Merwe, P. A.; Besra, G. S.; Jones, E. Y.; Batista, F. D.; Cerundolo, V. The Length of Lipids Bound to Human CD1d Molecules Modulates the Affinity of NKT Cell TCR and the Threshold of NKT Cell Activation. J Exp Med 2007, 204 (5), 1131–1144. https://doi.org/10.1084/jem.20062342.</ref>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="affinity"/><ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref name="affinity"/>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> *[[3gmq]]<br /> *[[4f7c]]<br /> <br /> == References ==<br /> {{Reflist}}<br /> <br /> </StructureSection></div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3354833 Sandbox Reserved 1660 2021-02-12T19:13:49Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <StructureSection load='3GMQ' size='350' 'frame'='true' side='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1'><br /> <br /> =='''Structure of mouse CD1d'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|190px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br><br /> <br /> == Structure ==<br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref>: <br><br /> :- an <scene name='86/868193/Alpha_chain/4'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> :- a <scene name='86/868193/Beta-2-microglobulin_chain/3'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/2'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/2'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/2'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="affinity"/><ref name="site"/><ref>McCarthy, C.; Shepherd, D.; Fleire, S.; Stronge, V. S.; Koch, M.; Illarionov, P. A.; Bossi, G.; Salio, M.; Denkberg, G.; Reddington, F.; Tarlton, A.; Reddy, B. G.; Schmidt, R. R.; Reiter, Y.; Griffiths, G. M.; van der Merwe, P. A.; Besra, G. S.; Jones, E. Y.; Batista, F. D.; Cerundolo, V. The Length of Lipids Bound to Human CD1d Molecules Modulates the Affinity of NKT Cell TCR and the Threshold of NKT Cell Activation. J Exp Med 2007, 204 (5), 1131–1144. https://doi.org/10.1084/jem.20062342.</ref>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="affinity"/><ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref name="affinity"/>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> *[[3gmq]]<br /> *[[4f7c]]<br /> <br /> == References ==<br /> {{Reflist}}<br /> <br /> </StructureSection></div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3354832 Sandbox Reserved 1660 2021-02-12T19:01:49Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <StructureSection load='3GMQ' size='350' 'frame'='true' side='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1'><br /> <br /> =='''Structure of mouse CD1d'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref>: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="affinity"/><ref name="site"/><ref>McCarthy, C.; Shepherd, D.; Fleire, S.; Stronge, V. S.; Koch, M.; Illarionov, P. A.; Bossi, G.; Salio, M.; Denkberg, G.; Reddington, F.; Tarlton, A.; Reddy, B. G.; Schmidt, R. R.; Reiter, Y.; Griffiths, G. M.; van der Merwe, P. A.; Besra, G. S.; Jones, E. Y.; Batista, F. D.; Cerundolo, V. The Length of Lipids Bound to Human CD1d Molecules Modulates the Affinity of NKT Cell TCR and the Threshold of NKT Cell Activation. J Exp Med 2007, 204 (5), 1131–1144. https://doi.org/10.1084/jem.20062342.</ref>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="affinity"/><ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref name="affinity"/>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> *[[3gmq]]<br /> *[[4f7c]]<br /> <br /> == References ==<br /> {{Reflist}}<br /> <br /> </StructureSection></div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342374 Sandbox Reserved 1660 2021-01-14T20:16:43Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref>: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="affinity"/><ref name="site"/><ref>McCarthy, C.; Shepherd, D.; Fleire, S.; Stronge, V. S.; Koch, M.; Illarionov, P. A.; Bossi, G.; Salio, M.; Denkberg, G.; Reddington, F.; Tarlton, A.; Reddy, B. G.; Schmidt, R. R.; Reiter, Y.; Griffiths, G. M.; van der Merwe, P. A.; Besra, G. S.; Jones, E. Y.; Batista, F. D.; Cerundolo, V. The Length of Lipids Bound to Human CD1d Molecules Modulates the Affinity of NKT Cell TCR and the Threshold of NKT Cell Activation. J Exp Med 2007, 204 (5), 1131–1144. https://doi.org/10.1084/jem.20062342.</ref>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="affinity"/><ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref name="affinity"/>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> *[[3gmq]]<br /> *[[4f7c]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342363 Sandbox Reserved 1660 2021-01-14T19:59:00Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref>: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="affinity"/><ref name="site"/><ref>McCarthy, C.; Shepherd, D.; Fleire, S.; Stronge, V. S.; Koch, M.; Illarionov, P. A.; Bossi, G.; Salio, M.; Denkberg, G.; Reddington, F.; Tarlton, A.; Reddy, B. G.; Schmidt, R. R.; Reiter, Y.; Griffiths, G. M.; van der Merwe, P. A.; Besra, G. S.; Jones, E. Y.; Batista, F. D.; Cerundolo, V. The Length of Lipids Bound to Human CD1d Molecules Modulates the Affinity of NKT Cell TCR and the Threshold of NKT Cell Activation. J Exp Med 2007, 204 (5), 1131–1144. https://doi.org/10.1084/jem.20062342.</ref>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="affinity"/><ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref name="affinity"/>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> *[[3gmq]]<br /> *[[4f7c]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342362 Sandbox Reserved 1660 2021-01-14T19:58:41Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref>: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids<ref name="Structure"/>. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="affinity"/><ref name="site"/><ref>McCarthy, C.; Shepherd, D.; Fleire, S.; Stronge, V. S.; Koch, M.; Illarionov, P. A.; Bossi, G.; Salio, M.; Denkberg, G.; Reddington, F.; Tarlton, A.; Reddy, B. G.; Schmidt, R. R.; Reiter, Y.; Griffiths, G. M.; van der Merwe, P. A.; Besra, G. S.; Jones, E. Y.; Batista, F. D.; Cerundolo, V. The Length of Lipids Bound to Human CD1d Molecules Modulates the Affinity of NKT Cell TCR and the Threshold of NKT Cell Activation. J Exp Med 2007, 204 (5), 1131–1144. https://doi.org/10.1084/jem.20062342.</ref>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="affinity"/><ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref name="affinity"/>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> *[[3gmq]]<br /> *[[4f7c]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342356 Sandbox Reserved 1660 2021-01-14T19:49:20Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref> <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids<ref name="Structure"/>. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="affinity"/><ref name="site"/><ref>McCarthy, C.; Shepherd, D.; Fleire, S.; Stronge, V. S.; Koch, M.; Illarionov, P. A.; Bossi, G.; Salio, M.; Denkberg, G.; Reddington, F.; Tarlton, A.; Reddy, B. G.; Schmidt, R. R.; Reiter, Y.; Griffiths, G. M.; van der Merwe, P. A.; Besra, G. S.; Jones, E. Y.; Batista, F. D.; Cerundolo, V. The Length of Lipids Bound to Human CD1d Molecules Modulates the Affinity of NKT Cell TCR and the Threshold of NKT Cell Activation. J Exp Med 2007, 204 (5), 1131–1144. https://doi.org/10.1084/jem.20062342.</ref>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="affinity"/><ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref name="affinity"/>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> *[[3gmq]]<br /> *[[4f7c]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342355 Sandbox Reserved 1660 2021-01-14T19:49:06Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref> <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids<ref name="Structure"/>. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="affinity"/><ref name="site"/><ref>McCarthy, C.; Shepherd, D.; Fleire, S.; Stronge, V. S.; Koch, M.; Illarionov, P. A.; Bossi, G.; Salio, M.; Denkberg, G.; Reddington, F.; Tarlton, A.; Reddy, B. G.; Schmidt, R. R.; Reiter, Y.; Griffiths, G. M.; van der Merwe, P. A.; Besra, G. S.; Jones, E. Y.; Batista, F. D.; Cerundolo, V. The Length of Lipids Bound to Human CD1d Molecules Modulates the Affinity of NKT Cell TCR and the Threshold of NKT Cell Activation. J Exp Med 2007, 204 (5), 1131–1144. https://doi.org/10.1084/jem.20062342.</ref>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="affinity"/><ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref name="affinity"/>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> *[[gmq]]<br /> *[[4f7c]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342354 Sandbox Reserved 1660 2021-01-14T19:48:50Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref> <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids<ref name="Structure"/>. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="affinity"/><ref name="site"/><ref>McCarthy, C.; Shepherd, D.; Fleire, S.; Stronge, V. S.; Koch, M.; Illarionov, P. A.; Bossi, G.; Salio, M.; Denkberg, G.; Reddington, F.; Tarlton, A.; Reddy, B. G.; Schmidt, R. R.; Reiter, Y.; Griffiths, G. M.; van der Merwe, P. A.; Besra, G. S.; Jones, E. Y.; Batista, F. D.; Cerundolo, V. The Length of Lipids Bound to Human CD1d Molecules Modulates the Affinity of NKT Cell TCR and the Threshold of NKT Cell Activation. J Exp Med 2007, 204 (5), 1131–1144. https://doi.org/10.1084/jem.20062342.</ref>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="affinity"/><ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref name="affinity"/>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> *[[GMQ]]<br /> *[[4F7C]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342348 Sandbox Reserved 1660 2021-01-14T19:46:02Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref> <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids<ref name="Structure"/>. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="affinity"/><ref name="site"/><ref>McCarthy, C.; Shepherd, D.; Fleire, S.; Stronge, V. S.; Koch, M.; Illarionov, P. A.; Bossi, G.; Salio, M.; Denkberg, G.; Reddington, F.; Tarlton, A.; Reddy, B. G.; Schmidt, R. R.; Reiter, Y.; Griffiths, G. M.; van der Merwe, P. A.; Besra, G. S.; Jones, E. Y.; Batista, F. D.; Cerundolo, V. The Length of Lipids Bound to Human CD1d Molecules Modulates the Affinity of NKT Cell TCR and the Threshold of NKT Cell Activation. J Exp Med 2007, 204 (5), 1131–1144. https://doi.org/10.1084/jem.20062342.</ref>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="affinity"/><ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref name="affinity"/>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342346 Sandbox Reserved 1660 2021-01-14T19:44:28Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref><ref>McCarthy, C.; Shepherd, D.; Fleire, S.; Stronge, V. S.; Koch, M.; Illarionov, P. A.; Bossi, G.; Salio, M.; Denkberg, G.; Reddington, F.; Tarlton, A.; Reddy, B. G.; Schmidt, R. R.; Reiter, Y.; Griffiths, G. M.; van der Merwe, P. A.; Besra, G. S.; Jones, E. Y.; Batista, F. D.; Cerundolo, V. The Length of Lipids Bound to Human CD1d Molecules Modulates the Affinity of NKT Cell TCR and the Threshold of NKT Cell Activation. J Exp Med 2007, 204 (5), 1131–1144. https://doi.org/10.1084/jem.20062342.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref> <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids<ref name="Structure"/>. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="affinity"/><ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref name="affinity"/>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342345 Sandbox Reserved 1660 2021-01-14T19:43:29Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref><ref>(1) McCarthy, C.; Shepherd, D.; Fleire, S.; Stronge, V. S.; Koch, M.; Illarionov, P. A.; Bossi, G.; Salio, M.; Denkberg, G.; Reddington, F.; Tarlton, A.; Reddy, B. G.; Schmidt, R. R.; Reiter, Y.; Griffiths, G. M.; van der Merwe, P. A.; Besra, G. S.; Jones, E. Y.; Batista, F. D.; Cerundolo, V. The Length of Lipids Bound to Human CD1d Molecules Modulates the Affinity of NKT Cell TCR and the Threshold of NKT Cell Activation. J Exp Med 2007, 204 (5), 1131–1144. https://doi.org/10.1084/jem.20062342.<ref/>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref> <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids<ref name="Structure"/>. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="affinity"/><ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref name="affinity"/>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342343 Sandbox Reserved 1660 2021-01-14T19:41:19Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref> <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids<ref name="Structure"/>. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="affinity"/><ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref name="affinity"/>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342340 Sandbox Reserved 1660 2021-01-14T19:35:27Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref> <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids<ref name="Structure"/>. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="affinity"/><ref name="site"/>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref><ref name="affinity"/>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref>Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342339 Sandbox Reserved 1660 2021-01-14T19:32:03Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref><ref name="affinity"/>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref> <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids<ref name="Structure"/>. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="site"/></ref><ref name="affinity"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="site"/><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref><ref name="affinity"/>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref>Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342327 Sandbox Reserved 1660 2021-01-14T19:19:50Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> '''[[CD1]] (Cluster of Differentiation 1)''' is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> '''CD1d protein''' is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref> <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids<ref name="Structure"/>. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="site"/><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref><ref name="affinity"/>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref>Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342324 Sandbox Reserved 1660 2021-01-14T19:18:36Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref> <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids<ref name="Structure"/>. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it<ref name="site"/><ref name="affinity">Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref><ref name="affinity"/>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref>Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342313 Sandbox Reserved 1660 2021-01-14T19:10:52Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref> <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids<ref name="Structure"/>. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices<ref name="site">Schiefner, A.; Fujio, M.; Wu, D.; Wong, C.-H.; Wilson, I. A. Structural Evaluation of Potent NKT-Cell Agonists: Implications for Design of Novel Stimulatory Ligands. J Mol Biol 2009, 394 (1), 71–82. https://doi.org/10.1016/j.jmb.2009.08.061</ref>.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR<ref name="site"/>.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref>Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328.</ref>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342303 Sandbox Reserved 1660 2021-01-14T19:02:17Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref> <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids<ref name="Structure"/>. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref>Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328</ref>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342301 Sandbox Reserved 1660 2021-01-14T19:01:12Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated<ref>Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Jan 14, 2021).</ref>. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref name="Immunity">Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref> <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids<ref name="Structure"/>. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections. They can also be protective in autoimmune diseases or cancer<ref name="Immunity"/><ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects<ref>Rossjohn, J., Pellicci, D. G., Patel, O., Gapin, L., & Godfrey, D. I. (2012). Recognition of CD1d-restricted antigens by natural killer T cells. Nature reviews. Immunology, 12(12), 845–857. https://doi.org/10.1038/nri3328</ref>.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3342279 Sandbox Reserved 1660 2021-01-14T18:31:38Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins<ref>Jullien, D.; Afanassieff, M.; Claudy, A.; Nicolas, J.; Kaiserlian, D. CD1 : une nouvelle famille de molécules présentatrices d’antigènes aux caractéristiques singulières. Med Sci (Paris) 1999, 15 (1), 7. https://doi.org/10.4267/10608/1190.</ref>. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the [https://en.wikipedia.org/wiki/Immune_system immune system]. It is involved in presenting a lipid antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of [https://en.wikipedia.org/wiki/Antigen-presenting_cell APC cells]. When the recognition between the CD1d bound to its lipid ligand and the [[TCR]] of a NKT cell occurs, the [https://en.wikipedia.org/wiki/Lymphocyte lymphocyte] turns out to be activated<ref>Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Jan 14, 2021).</ref>. Thus, the production of cytotoxic molecules such as Th1, Th2, [[interleukin]]-4 and [https://en.wikipedia.org/wiki/Interferon_gamma INF-gamma] is triggered by this activation<ref>Joyce, S. CD1d and Natural T Cells: How Their Properties Jump-Start the Immune System. CMLS, Cell. Mol. Life Sci. 2001, 58 (3), 442–469. https://doi.org/10.1007/PL00000869.</ref>. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to [https://en.wikipedia.org/wiki/Autoimmune_disease autoimmune diseases] and [https://en.wikipedia.org/wiki/Cancer cancers]. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules<ref>Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids<ref name="Structure">Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ (accessed Dec 5, 2020).</ref> <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids<ref name="Structure"/>. <br><br><br /> The first chain is made of two [https://en.wikipedia.org/wiki/Beta_sheet beta-sheets] and a set of 2 [[alpha helix]]. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via [https://en.wikipedia.org/wiki/N-linked_glycosylation N-glycosylations] and three types of small molecules bound to that protein<ref name="Structure"/>. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the [https://en.wikipedia.org/wiki/Cytokine cytokine] release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against [https://en.wikipedia.org/wiki/Malaria malaria] or resulting in a more rapid clearance of certain [https://en.wikipedia.org/wiki/Virus virus] infections<ref>Sköld, M.; Behar, S. M. Role of CD1d-Restricted NKT Cells in Microbial Immunity. Infect Immun 2003, 71 (10), 5447–5455. https://doi.org/10.1128/IAI.71.10.5447-5455.2003.</ref>. They can also be protective in autoimmune diseases or cancer<ref>Brutkiewicz, R. R. CD1d Ligands: The Good, the Bad, and the Ugly. The Journal of Immunology 2006, 177 (2), 769–775. https://doi.org/10.4049/jimmunol.177.2.769.</ref>.<br /> </p><br /> <br /> <p align="justify"><br /> The presence of high amount of CD1d proteins on the cell surface of NKT cells gives rise to a novel type of NKT cells. This larger amount of CD1d proteins allows the Cd1d high NKT cells to bind more alpha-galactosylceramide molecules and therefore to can produce greater levels of interleukin-4 and INF-gamma molecules leading to possible therapeutical effects.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become [https://en.wikipedia.org/wiki/Fluorescence fluorescent] by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted<ref>Benlagha, K., Weiss, A., Beavis, A., Teyton, L., & Bendelac, A. (2000). In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. The Journal of experimental medicine, 191(11), 1895–1903. https://doi.org/10.1084/jem.191.11.1895</ref>. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341566 Sandbox Reserved 1660 2021-01-11T17:41:59Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC cells. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to autoimmune diseases and cancers. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341559 Sandbox Reserved 1660 2021-01-11T17:32:21Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC cells. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to autoimmune diseases and cancers. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/4'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=File:CD1d_dependent_lipid_antigen_presentation.jpg&diff=3341558 File:CD1d dependent lipid antigen presentation.jpg 2021-01-11T17:20:04Z

<p>Christophe Zhuge: </p> <hr /> <div>== Licensing ==<br /> {{subst:Non-commercial from license selector}}<br /> The final, published version of this article is available at https://air.unimi.it/retrieve/handle/2434/246210/334044/phd_unimi_R09699.pdf</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341506 Sandbox Reserved 1660 2021-01-10T20:48:17Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC cells. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to autoimmune diseases and cancers. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_4f7c_u4681/1'>Conformational variations</scene> between CD1d no ligand and structure of bovine CD1d with bound C12-di-sulfatide.<br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341501 Sandbox Reserved 1660 2021-01-10T20:34:59Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC cells. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to autoimmune diseases and cancers. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <scene name='86/868193/Morph_3gmq_3gmn_u4681/5'>Conformational variations</scene><br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341495 Sandbox Reserved 1660 2021-01-10T19:57:44Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC cells. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to autoimmune diseases and cancers. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341492 Sandbox Reserved 1660 2021-01-10T19:56:42Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> [[Image:CD1d dependent lipid antigen presentation.jpg | thumb ||left|200px|'''CD1d dependent lipid antigen presentation.''']]<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC cells. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to autoimmune diseases and cancers. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=File:CD1d_dependent_lipid_antigen_presentation.jpg&diff=3341489 File:CD1d dependent lipid antigen presentation.jpg 2021-01-10T19:48:24Z

<p>Christophe Zhuge: </p> <hr /> <div>== Licensing ==<br /> {{subst:Non-commercial from license selector}}<br /> The final, published version of this article is available at http://www.karger.com/?doi=351034</div>

Christophe Zhuge https://proteopedia.org/index.php?title=File:CD1d_dependent_lipid_antigen_presentation.jpg&diff=3341485 File:CD1d dependent lipid antigen presentation.jpg 2021-01-10T19:39:37Z

<p>Christophe Zhuge: </p> <hr /> <div>== Licensing ==<br /> {{subst:Non-commercial from license selector}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=File:CD1d_dependent_lipid_antigen_presentation.jpg&diff=3341479 File:CD1d dependent lipid antigen presentation.jpg 2021-01-10T19:24:58Z

<p>Christophe Zhuge: </p> <hr /> <div>== Licensing ==<br /> {{subst:No license from license selector|Somewebsite}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341476 Sandbox Reserved 1660 2021-01-10T19:04:38Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC cells. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to autoimmune diseases and cancers. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This <scene name='86/868193/Site/1'>site</scene> is located at the A and F pockets in the region of the alpha helices.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variations that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> <p align="justify"><br /> CD1d proteins lipid recognition is based on the interaction of the protein with its ligand. Nevertheless, the recognition relies on two recognitions. The first one is the recognition of the head of the lipid and the second one is the recognition of the length of the molecule. Because there are more than one condition to fill in order to interact with CD1d proteins, the affinity for a lipid depends itself on a plurality of parameters which modulates it.<br /> </p><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341444 Sandbox Reserved 1660 2021-01-10T17:20:29Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC cells. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to autoimmune diseases and cancers. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two <scene name='86/868193/Oligosaccharides/1'>oligosaccharides</scene> bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.The recognition between the protein and its ligand occurs at a specific spot which creates an appropriate environment for the interaction to happen. This site is located at the A and F pockets in the region of the alpha helices.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in the immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variation that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341437 Sandbox Reserved 1660 2021-01-10T17:07:18Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='86/868193/Cd1d/1' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC cells. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to autoimmune diseases and cancers. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two oligosaccharides bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variation that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341436 Sandbox Reserved 1660 2021-01-10T17:05:10Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of <scene name='86/868193/Cd1d/1'>CD1d</scene> and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC cells. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation. Therefore, CD1d proteins are precursors of the adaptive immune reaction which are key activators of the NKT cells. As a result, a deficiency of CD1d proteins may lead to a deficiency of the NKT cells functioning and thus to autoimmune diseases and cancers. <br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. Thus, it limits the risk of other similar molecules or binding CD1d proteins and ensures that the immune response is accurate. Among these molecules are included glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules.<br /> </p><br /> <br /> == Structure ==<br /> <Structure load='' 'frame'='true' align='right' size='300' side='right' caption=''/><br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand binds between the two alpha-helices.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two oligosaccharides bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell T cells] (which play a central role in immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variation that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341425 Sandbox Reserved 1660 2021-01-10T16:44:23Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to [https://en.wikipedia.org/wiki/Natural_killer_T_cell: NKT cells]. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of <scene name='86/868193/Cd1d/1'>CD1d</scene> and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC cells. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation.<br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. These include glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules.<br /> </p><br /> <br /> == Structure ==<br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/3'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/2'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand bind between the two alpha-helix.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two oligosaccharides bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to [[Major Histocompatibility Complex Class I]], but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of [https://en.wikipedia.org/wiki/T_cell: T cells] (which play a central role in immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variation that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341416 Sandbox Reserved 1660 2021-01-10T16:35:03Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> [[CD1]] (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to NKT cells. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of <scene name='86/868193/Cd1d/1'>CD1d</scene> and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation.<br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. These include glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules.<br /> </p><br /> <br /> == Structure ==<br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/2'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/1'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand bind between the two alpha-helix.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two oligosaccharides bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to MHC class I, but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of T cells (which play a central role in immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variation that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341410 Sandbox Reserved 1660 2021-01-10T16:24:14Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> CD1 (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to NKT cells. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation.<br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. These include glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules.<br /> </p><br /> <br /> == Structure ==<br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an <scene name='86/868193/Alpha_chain/2'>alpha chain</scene> (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a <scene name='86/868193/Beta-2-microglobulin_chain/1'>beta-2-microglobulin chain</scene> of 99 amino acids. <br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> The ligand bind between the two alpha-helix.<br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two oligosaccharides bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to MHC class I, but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of T cells (which play a central role in immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variation that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341387 Sandbox Reserved 1660 2021-01-10T15:28:54Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> CD1 (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to NKT cells. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation.<br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. These include glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules.<br /> </p><br /> <br /> == Structure ==<br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an alpha chain (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a beta-2-microglobulin chain of 99 amino acids. <br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two oligosaccharides bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to MHC class I, but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of T cells (which play a central role in immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variation that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> <ref>{{Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added [https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ] (accessed Dec 5, 2020).}}</ref><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341385 Sandbox Reserved 1660 2021-01-10T15:27:34Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> CD1 (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to NKT cells. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation.<br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands that can be presented by CD1d to NKT or other CD1d-restricted T cells are very specific. Only a narrow set of molecules can bind its recognition site. These include glycolipids from a marine sponge, bacterial glycolipids, normal endogenous glycolipids, tumor-derived phospholipids and glycolipids, and nonlipidic molecules.<br /> </p><br /> <br /> == Structure ==<br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an alpha chain (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a beta-2-microglobulin chain of 99 amino acids. <br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two oligosaccharides bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to MHC class I, but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of T cells (which play a central role in immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variation that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> <ref>{{Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added [https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ] (accessed Dec 5, 2020).}}</ref><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> <p align="justify"><br /> The presentation of many of ligands can have immunopotentiating effects, such as serving as an adjuvant against malaria or resulting in a more rapid clearance of certain virus infections. They can also be protective in autoimmune diseases or cancer.<br /> </p><br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341381 Sandbox Reserved 1660 2021-01-10T15:10:37Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> CD1 (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to NKT cells. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> CD1d protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation.<br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands of CD1d protein are very specific. Only a narrow set of molecules can bind its recognition site. Amongst those molecules are aplhaGalCer, alpha glucuronyl ceramide acid, alpha galacturonyl ceramide acid, IGb3 and HS44.<br /> </p><br /> <br /> == Structure ==<br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an alpha chain (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a beta-2-microglobulin chain of 99 amino acids. <br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two oligosaccharides bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. CD1d molecules are structurally similar to MHC class I, but present lipid antigens as opposed to peptides and the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of T cells (which play a central role in immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variation that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> <ref>{{Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added [https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ] (accessed Dec 5, 2020).}}</ref><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341375 Sandbox Reserved 1660 2021-01-10T14:55:41Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry : [https://www.rcsb.org/structure/3GMQ 3GMQ])' scene='' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> CD1 (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to NKT cells. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> 3GMQ protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation.<br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands of CD1d protein are very specific. Only a narrow set of molecules can bind its recognition site. Amongst those molecules are aplhaGalCer, alpha glucuronyl ceramide acid, alpha galacturonyl ceramide acid, IGb3 and HS44.<br /> </p><br /> <br /> == Structure ==<br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an alpha chain (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a beta-2-microglobulin chain of 99 amino acids. <br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two oligosaccharides bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. The overall structure of CD1d protein is akin to class I MHC’s molecules. Notwithstanding, the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of T cells (which play a central role in immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variation that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> <ref>{{Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added [https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ] (accessed Dec 5, 2020).}}</ref><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341374 Sandbox Reserved 1660 2021-01-10T14:52:33Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry [https://www.rcsb.org/structure/3GMQ : 3GMQ])' scene='' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> CD1 (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to NKT cells. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> 3GMQ protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation.<br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands of CD1d protein are very specific. Only a narrow set of molecules can bind its recognition site. Amongst those molecules are aplhaGalCer, alpha glucuronyl ceramide acid, alpha galacturonyl ceramide acid, IGb3 and HS44.<br /> </p><br /> <br /> == Structure ==<br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an alpha chain (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a beta-2-microglobulin chain of 99 amino acids. <br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two oligosaccharides bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. The overall structure of CD1d protein is akin to class I MHC’s molecules. Notwithstanding, the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of T cells (which play a central role in immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variation that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> <ref>{{Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added [https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ] (accessed Dec 5, 2020).}}</ref><br /> <br /> == Applications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341372 Sandbox Reserved 1660 2021-01-10T14:50:06Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry [https://www.rcsb.org/structure/3GMQ : 3GMQ])' scene='' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> CD1 (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to NKT cells. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> 3GMQ protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation.<br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands of CD1d protein are very specific. Only a narrow set of molecules can bind its recognition site. Amongst those molecules are aplhaGalCer, alpha glucuronyl ceramide acid, alpha galacturonyl ceramide acid, IGb3 and HS44.<br /> </p><br /> <br /> == Structure ==<br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an alpha chain (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a beta-2-microglobulin chain of 99 amino acids. <br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> </p><br /> <br /> <p align="justify"><br /> Additionally, there are two oligosaccharides bound to the alpha chain via N-glycosylations and three types of small molecules bound to that protein. The overall structure of CD1d protein is akin to class I MHC’s molecules. Notwithstanding, the cleft where the ligand can bind its protein is different between MHC molecules and CD1d molecules. Indeed, the hydrophobic cleft of CD1d has a narrow opening.<br /> </p><br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of T cells (which play a central role in immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variation that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> <ref>{{Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added [https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ] (accessed Dec 5, 2020).}}</ref><br /> <br /> == Appications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341371 Sandbox Reserved 1660 2021-01-10T14:45:56Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry [https://www.rcsb.org/structure/3GMQ : 3GMQ])' scene='' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> CD1 (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to NKT cells. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> 3GMQ protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation.<br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands of CD1d protein are very specific. Only a narrow set of molecules can bind its recognition site. Amongst those molecules are aplhaGalCer, alpha glucuronyl ceramide acid, alpha galacturonyl ceramide acid, IGb3 and HS44.<br /> </p><br /> <br /> == Structure ==<br /> <br /> <p align="justify"><br /> CD1d protein is made of 2 chains: <br><br /> ::- an alpha chain (T-cell surface glycoprotein CD1d1) of 287 amino acids <br><br /> ::- a beta-2-microglobulin chain of 99 amino acids. <br><br /> The first chain is made of two beta-sheets and a set of 2 alpha-helices. Each beta-sheet contains four antiparallel strands. <br>The total molecular weight of the alpha chain is 33 kDa when not associated to any oligosaccharide and 55 kDa when the five oligosaccharides are associated to the chain. <br /> </p><br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of T cells (which play a central role in immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variation that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> <ref>{{Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added [https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ] (accessed Dec 5, 2020).}}</ref><br /> <br /> == Appications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341370 Sandbox Reserved 1660 2021-01-10T14:35:29Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry [https://www.rcsb.org/structure/3GMQ : 3GMQ])' scene='' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> CD1 (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to NKT cells. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> 3GMQ protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation.<br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands of CD1d protein are very specific. Only a narrow set of molecules can bind its recognition site. Amongst those molecules are aplhaGalCer, alpha glucuronyl ceramide acid, alpha galacturonyl ceramide acid, IGb3 and HS44.<br /> </p><br /> <br /> == Structure ==<br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of T cells (which play a central role in immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variation that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> <ref>{{Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added [https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ] (accessed Dec 5, 2020).}}</ref><br /> <br /> == Appications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341368 Sandbox Reserved 1660 2021-01-10T14:33:57Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry [https://www.rcsb.org/structure/3GMQ : 3GMQ])' scene='' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> CD1 (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to NKT cells. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> ==== Role in the immune system ====<br /> <br /> <p align="justify"><br /> 3GMQ protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation.<br /> </p><br /> <br /> ==== Ligands presented by CD1d ====<br /> <br /> <p align="justify"><br /> The ligands of CD1d protein are very specific. Only a narrow set of molecules can bind its recognition site. Amongst those molecules are aplhaGalCer, alpha glucuronyl ceramide acid, alpha galacturonyl ceramide acid, IGb3 and HS44.<br /> </p><br /> <br /> == Structure ==<br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> ==== Conformational variation ====<br /> <br /> <p align="justify"><br /> NTK cells are a subset of T cells (which play a central role in immune response) that are activated by CD1d-glycolipid complexes. α-GalCer is a potent NKT cell agonist when presented by CD1d. The stability of the CD1d-glycolipid complexes has an impact on the cytokine release (cell signaling). Conformational variation that would stabilize the F’-pocket (primary site of interaction with the T cell receptor, NKT TCR) might increase CD1d affinity for the NKT TCR.<br /> </p><br /> <br /> ==== CD1d affinity ====<br /> <br /> <ref>{{Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added [https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ] (accessed Dec 5, 2020).}}</ref><br /> <br /> == Appications ==<br /> <br /> ==== Immunotherapeutic tool ====<br /> <br /> ==== NKT cells marker ====<br /> <br /> <p align="justify"><br /> CD1 molecules can also be used as NKT cell markers. Indeed, a CD1 molecule can be engineered to become fluorescent by binding a fluorescent-potent molecule to it. When the engineered complex interacts with a NKT cell, the fluorescent signal is emitted and therefore the NKT cells can be spotted. <br /> </p><br /> <br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==</div>

Christophe Zhuge https://proteopedia.org/index.php?title=Sandbox_Reserved_1660&diff=3341367 Sandbox Reserved 1660 2021-01-10T14:29:51Z

<p>Christophe Zhuge: </p> <hr /> <div>{{Sandbox_Reserved_ESBS20_}} <br /> <br /> <Structure load='3GMQ' size='350' 'frame'='true' align='right' caption='Structure of mouse CD1d expressed in SF9 cells, no ligand added (PDB entry [https://www.rcsb.org/structure/3GMQ : 3GMQ])' scene='' /><br /> <br /> =='''Structure of mouse CD1d expressed in SF9 cells, no ligand added'''==<br /> <br /> <p align="justify"><br /> CD1 (Cluster of Differentiation 1) is a family of glycoproteins involved in the presentation of antigens on the surface of specific cells to NKT cells. Amongst these CD1-presenting cells can be counted splenic dendritic cells, marginal zone B cells and CD4+CD8+ thymocytes. This family is made of two main groups: group 1 is composed of CD1a, b and c proteins and group 2 is composed of CD1d proteins. <br /> <br><br /> Thus, the structure and function of such proteins in mice are akin to those of humans. Mice doesn’t express group 1 CD1 molecules. Instead, they have two kinds of CD1d molecules. Therefore, they have been widely used to characterize the functions of CD1d and CD1d-dependent NKT cells in many diseases.<br /> </p><br /> <br /> <br /> __TOC__<br /> <br /> == Function ==<br /> <br /> === Role in the immune system ===<br /> <br /> <p align="justify"><br /> 3GMQ protein is a molecule of the immune system. It is involved in presenting a lipidic antigen to NKT cells. Indeed, these proteins are located on the surface of the plasma membrane of APC. When the recognition between the CD1d bound to its lipidic ligand and the TCR of a NKT cell occurs, the lymphocyte turns out to be activated. Thus, the production of cytotoxic molecules such as Th1, Th2, interleukin-4 and INF-gamma is triggered by this activation.<br /> </p><br /> <br /> === Ligands presented by CD1d ===<br /> <br /> <p align="justify"><br /> The ligands of CD1d protein are very specific. Only a narrow set of molecules can bind its recognition site. Amongst those molecules are aplhaGalCer, alpha glucuronyl ceramide acid, alpha galacturonyl ceramide acid, IGb3 and HS44.<br /> </p><br /> <br /> == Structure ==<br /> <br /> <br /> == Impact of ligand-binding ==<br /> <br /> === Conformational variation ===<br /> <br /> === CD1d affinity ===<br /> <br /> <ref>{{Information, N. C. for B.; Pike, U. S. N. L. of M. R.; BethesdaMD; 20894USA. 3GMQ: Structure of mouse CD1d expressed in SF9 cells, no ligand added [https://www.ncbi.nlm.nih.gov/Structure/pdb/3GMQ] (accessed Dec 5, 2020).}}</ref><br /> <br /> == Appications ==<br /> <br /> === Immunotherapeutic tool ===<br /> <br /> === NKT cells marker ===<br /> <br /> ==See Also==<br /> *[[CD1|CD1]]<br /> <br /> == References ==<br /> {{Reflist}}<br /> <br /> This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.<br /> <br /> </StructureSection><br /> == References ==</div>

Christophe Zhuge