7s8a - Revision history

OCA at 06:45, 21 November 2024

2024-11-21T06:45:57Z

← Older revision		Revision as of 06:45, 21 November 2024
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	</table>		</table>
	== Disease ==		== Disease ==
	[https://www.uniprot.org/uniprot/HLAB_HUMAN HLAB_HUMAN] ~~Prediction of allopurinol toxicity;NON RARE IN EUROPE: Ankylosing spondylitis;Prediction of flucloxacilline toxicity;~~Giant cell arteritis;Takayasu arteritis;~~Reactive arthritis;Behcet~~ disease;Stevens-Johnson syndrome;~~Prediction of phenytoin or carbamazepine toxicity~~;~~Pulmonary arterial hypertension associated with connective tissue disease~~;~~Prediction of abacavir toxicity~~. Disease susceptibility is associated with variants affecting the gene represented in this entry. Increased susceptibility to Stevens-Johnson syndrome is conferred by allele B15:02.<ref>PMID:15057820</ref> Disease susceptibility is associated with variants affecting the gene represented in this entry. A restricted number of HLA-B27 subtypes can be associated with ankylosing spondylitis and other B27-related diseases, and an elevated frequency of the B27:02 allele in ankylosing spondylitis patients is identified. The allele B27:07 seems to have a protective role in some populations because it was found only in the healthy controls.<ref>PMID:15603872</ref> There is evidence that HLA-B51 is associated with susceptibility to Behcet disease (BD). However, it is not certain whether HLA-B51 itself or a closely linked gene is responsible for susceptibility. The world distribution of HLA-B51 in healthy people corresponds to the global distribution of BD; in Southern hemisphere countries (Africa, South Pacific, etc.) and in some parts of Europe, the prevalence of HLA-B51 in healthy people is low or null, corresponding to a low prevalence of BD. The wide variation that exists in the relative risk of HLA-B51 would support other nongenetic risk factors.<ref>PMID:23291587</ref> The presence of allele B57:01 is associated with increased susceptibility to abacavir hypersensitivity [MIM:[https://omim.org/entry/142830 142830] in HIV-1 patients.<ref>PMID:11888582</ref> Allele group B08 is associated with increased susceptibility to rheumatoid arthritis, where affected individuals have antibodies to cyclic citrullinated peptide (anti-CCP-positive rheumatoid arthritis).<ref>PMID:22286218</ref>		[https://www.uniprot.org/uniprot/HLAB_HUMAN HLAB_HUMAN] Giant cell arteritis;Takayasu arteritis;Pulmonary arterial hypertension associated with connective tissue disease;Stevens-Johnson syndrome;Behcet disease;Reactive arthritis;NON RARE IN EUROPE: Ankylosing spondylitis. Disease susceptibility is associated with variants affecting the gene represented in this entry. Increased susceptibility to Stevens-Johnson syndrome is conferred by allele B15:02.<ref>PMID:15057820</ref> Disease susceptibility is associated with variants affecting the gene represented in this entry. A restricted number of HLA-B27 subtypes can be associated with ankylosing spondylitis and other B27-related diseases, and an elevated frequency of the B27:02 allele in ankylosing spondylitis patients is identified. The allele B27:07 seems to have a protective role in some populations because it was found only in the healthy controls.<ref>PMID:15603872</ref> There is evidence that HLA-B51 is associated with susceptibility to Behcet disease (BD). However, it is not certain whether HLA-B51 itself or a closely linked gene is responsible for susceptibility. The world distribution of HLA-B51 in healthy people corresponds to the global distribution of BD; in Southern hemisphere countries (Africa, South Pacific, etc.) and in some parts of Europe, the prevalence of HLA-B51 in healthy people is low or null, corresponding to a low prevalence of BD. The wide variation that exists in the relative risk of HLA-B51 would support other nongenetic risk factors.<ref>PMID:23291587</ref> The presence of allele B57:01 is associated with increased susceptibility to abacavir hypersensitivity [MIM:[https://omim.org/entry/142830 142830] in HIV-1 patients.<ref>PMID:11888582</ref> Allele group B08 is associated with increased susceptibility to rheumatoid arthritis, where affected individuals have antibodies to cyclic citrullinated peptide (anti-CCP-positive rheumatoid arthritis).<ref>PMID:22286218</ref>
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/HLAB_HUMAN HLAB_HUMAN] Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-B-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:25808313, PubMed:29531227, PubMed:9620674~~, PubMed:23209413~~). May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usually inactivated to prevent autoreactivity (PubMed:~~7743181~~, PubMed:~~18991276~~). Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells (PubMed:~~29531227~~, PubMed:~~9620674~~, PubMed:~~24600035~~). Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via constitutive proteasome and IFNG-induced immunoproteasome (PubMed:23209413). Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9 (PubMed:25808313, PubMed:29531227).<ref>PMID:18991276</ref> <ref>PMID:23209413</ref> <ref>PMID:24600035</ref> <ref>PMID:25808313</ref> <ref>PMID:29531227</ref> <ref>PMID:7743181</ref> <ref>PMID:9620674</ref> Allele B07:02: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and mainly a Leu anchor residue at the C-terminus (PubMed:7743181). Presents a long peptide (APRGPHGGAASGL) derived from the cancer-testis antigen CTAG1A/NY-ESO-1, eliciting a polyclonal CD8-positive T cell response against tumor cells (PubMed:29531227). Presents viral epitopes derived from HIV-1 gag-pol (TPQDLNTML) and Nef (RPQVPLRPM) (PubMed:25808313). Presents an immunodominant epitope derived from SARS-CoV-2 N/nucleoprotein (SPRWYFYYL) (PubMed:32887977). Displays self-peptides including a peptide derived from the signal sequence of HLA-DPB1 (APRTVALTA) (PubMed:7743181).<ref>PMID:25808313</ref> <ref>PMID:29531227</ref> <ref>PMID:32887977</ref> <ref>PMID:7743181</ref> Allele B08:01: Presents to CD8-positive T cells viral epitopes derived from EBV/HHV-4 EBNA3 (QAKWRLQTL), eliciting cytotoxic T cell response.<ref>PMID:9620674</ref> Allele B13:02: Presents multiple HIV-1 epitopes derived from gag (RQANFLGKI, GQMREPRGSDI), nef (RQDILDLWI), gag-pol (RQYDQILIE, GQGQWTYQI) and rev (LQLPPLERL), all having in common a Gln residue at position 2 and mainly hydrophobic amino acids Leu, Ile or Val at the C-terminus. Associated with succesful control of HIV-1 infection.<ref>PMID:17251285</ref> Allele B18:01: Preferentially presents octomeric and nonameric peptides sharing a common motif, namely a Glu at position 2 and Phe or Tyr anchor residues at the C-terminus (PubMed:14978097, PubMed:~~23749632~~, PubMed:~~18991276~~). Presents an EBV/HHV-4 epitope derived from BZLF1 (SELEIKRY) (PubMed:23749632). May present to CD8-positive T cells an antigenic peptide derived from MAGEA3 (MEVDPIGHLY), triggering an anti-tumor immune response (PubMed:12366779). May display a broad repertoire of self-peptides with a preference for peptides derived from RNA-binding proteins (PubMed:14978097).<ref>PMID:12366779</ref> <ref>PMID:14978097</ref> <ref>PMID:18991276</ref> <ref>PMID:23749632</ref> Allele B27:05: Presents to CD8-positive T cells immunodominant viral epitopes derived from HCV POLG (ARMILMTHF), HIV-1 gag (KRWIILGLNK), IAV NP (SRYWAIRTR), SARS-CoV-2 N/nucleoprotein (QRNAPRITF), EBV/HHV-4 EBNA4 (HRCQAIRKK) and EBV/HHV-4 EBNA6 (RRIYDLIEL), ~~confering~~ longterm protection against viral infection (PubMed:~~19139562~~, PubMed:18385228, PubMed:~~15113903~~, PubMed:~~9620674~~, PubMed:~~32887977~~). Can present self-peptides derived from cytosolic and nuclear proteins. All peptides carry an Arg at position 2 (PubMed:1922338). The peptide-bound form interacts with NK cell inhibitory receptor KIR3DL1 and inhibits NK cell activation in a peptide-specific way, being particularly sensitive to the nature of the amino acid side chain at position 8 of the antigenic peptide (PubMed:~~8879234~~, PubMed:~~15657948~~). KIR3DL1 fails to recognize HLA-B27:05 in complex with B2M and EBV/HHV-4 EBNA6 (RRIYDLIEL) peptide, which can lead to increased activation of NK cells during infection (PubMed:15657948). May present an altered repertoire of peptides in the absence of TAP1-TAP2 and TAPBPL (PubMed:9620674).<ref>PMID:15113903</ref> <ref>PMID:15657948</ref> <ref>PMID:18385228</ref> <ref>PMID:19139562</ref> <ref>PMID:1922338</ref> <ref>PMID:8879234</ref> <ref>PMID:9620674</ref> Allele B40:01: Presents immunodominant viral epitopes derived from EBV/HHV-4 LMP2 (IEDPPFNSL) and SARS-CoV-2 N/nucleoprotein (MEVTPSGTWL), triggering memory CD8-positive T cell response (PubMed:18991276, PubMed:32887977). Displays self-peptides sharing a signature motif, namely a Glu at position 2 and a Leu anchor residue at the C-terminus (PubMed:18991276).<ref>PMID:18991276</ref> <ref>PMID:32887977</ref> Allele B41:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B44:02: Presents immunodominant viral epitopes derived from EBV/HHV-4 EBNA4 (VEITPYKPTW) and EBNA6 (AEGGVGWRHW, EENLLDFVRF), triggering memory CD8-positive T cell response (PubMed:~~9620674~~, PubMed:~~18991276~~). Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Phe, Tyr or Trp anchor residues at the C-terminus (PubMed:18991276).<ref>PMID:18991276</ref> <ref>PMID:9620674</ref> Allele B45:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B46:01: Preferentially presents nonameric peptides sharing a signature motif, namely Ala and Leu at position 2 and Tyr, Phe, Leu, or Met anchor residues at the C-terminus. The peptide-bound form interacts with KIR2DL3 and inhibits NK cell cytotoxic response in a peptide-specific way.<ref>PMID:28514659</ref> Allele B47:01: Displays self-peptides sharing a signature motif, namely an Asp at position 2 and Leu or Met anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B49:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ile or Val anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B50:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B51:01: Presents an octomeric HIV-1 epitope derived from gag-pol (TAFTIPSI) to the public TRAV17/TRBV7-3 TCR clonotype, strongly suppressing HIV-1 replication.<ref>PMID:24600035</ref> Allele B54:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B55:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B56:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B57:01: The peptide-bound form recognizes KIR3DL1 and inhibits NK cell cytotoxic response.<ref>~~PMID:22020283</ref> <ref>~~PMID:25480565</ref> Allele B67:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Leu anchor residue at the C-terminus.<ref>PMID:7743181</ref>		[https://www.uniprot.org/uniprot/HLAB_HUMAN HLAB_HUMAN] Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-B-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:23209413, PubMed:25808313, PubMed:29531227, PubMed:9620674). May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usually inactivated to prevent autoreactivity (PubMed:18991276, PubMed:7743181). Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells (PubMed:24600035, PubMed:29531227, PubMed:9620674). Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via constitutive proteasome and IFNG-induced immunoproteasome (PubMed:23209413). Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9 (PubMed:25808313, PubMed:29531227).<ref>PMID:18991276</ref> <ref>PMID:23209413</ref> <ref>PMID:24600035</ref> <ref>PMID:25808313</ref> <ref>PMID:29531227</ref> <ref>PMID:7743181</ref> <ref>PMID:9620674</ref> Allele B07:02: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and mainly a Leu anchor residue at the C-terminus (PubMed:7743181). Presents a long peptide (APRGPHGGAASGL) derived from the cancer-testis antigen CTAG1A/NY-ESO-1, eliciting a polyclonal CD8-positive T cell response against tumor cells (PubMed:29531227). Presents viral epitopes derived from HIV-1 gag-pol (TPQDLNTML) and Nef (RPQVPLRPM) (PubMed:25808313). Presents an immunodominant epitope derived from SARS-CoV-2 N/nucleoprotein (SPRWYFYYL) (PubMed:32887977). Displays self-peptides including a peptide derived from the signal sequence of HLA-DPB1 (APRTVALTA) (PubMed:7743181).<ref>PMID:25808313</ref> <ref>PMID:29531227</ref> <ref>PMID:32887977</ref> <ref>PMID:7743181</ref> Allele B08:01: Presents to CD8-positive T cells viral epitopes derived from EBV/HHV-4 EBNA3 (QAKWRLQTL), eliciting cytotoxic T cell response.<ref>PMID:9620674</ref> Allele B13:02: Presents multiple HIV-1 epitopes derived from gag (RQANFLGKI, GQMREPRGSDI), nef (RQDILDLWI), gag-pol (RQYDQILIE, GQGQWTYQI) and rev (LQLPPLERL), all having in common a Gln residue at position 2 and mainly hydrophobic amino acids Leu, Ile or Val at the C-terminus. Associated with succesful control of HIV-1 infection.<ref>PMID:17251285</ref> Allele B18:01: Preferentially presents octomeric and nonameric peptides sharing a common motif, namely a Glu at position 2 and Phe or Tyr anchor residues at the C-terminus (PubMed:14978097, PubMed:18991276, PubMed:23749632). Presents an EBV/HHV-4 epitope derived from BZLF1 (SELEIKRY) (PubMed:23749632). May present to CD8-positive T cells an antigenic peptide derived from MAGEA3 (MEVDPIGHLY), triggering an anti-tumor immune response (PubMed:12366779). May display a broad repertoire of self-peptides with a preference for peptides derived from RNA-binding proteins (PubMed:14978097).<ref>PMID:12366779</ref> <ref>PMID:14978097</ref> <ref>PMID:18991276</ref> <ref>PMID:23749632</ref> Allele B27:05: Presents to CD8-positive T cells immunodominant viral epitopes derived from HCV POLG (ARMILMTHF), HIV-1 gag (KRWIILGLNK), IAV NP (SRYWAIRTR), SARS-CoV-2 N/nucleoprotein (QRNAPRITF), EBV/HHV-4 EBNA4 (HRCQAIRKK) and EBV/HHV-4 EBNA6 (RRIYDLIEL), conferring longterm protection against viral infection (PubMed:15113903, PubMed:18385228, PubMed:19139562, PubMed:32887977, PubMed:9620674). Can present self-peptides derived from cytosolic and nuclear proteins. All peptides carry an Arg at position 2 (PubMed:1922338). The peptide-bound form interacts with NK cell inhibitory receptor KIR3DL1 and inhibits NK cell activation in a peptide-specific way, being particularly sensitive to the nature of the amino acid side chain at position 8 of the antigenic peptide (PubMed:15657948, PubMed:8879234). KIR3DL1 fails to recognize HLA-B27:05 in complex with B2M and EBV/HHV-4 EBNA6 (RRIYDLIEL) peptide, which can lead to increased activation of NK cells during infection (PubMed:15657948). May present an altered repertoire of peptides in the absence of TAP1-TAP2 and TAPBPL (PubMed:9620674).<ref>PMID:15113903</ref> <ref>PMID:15657948</ref> <ref>PMID:18385228</ref> <ref>PMID:19139562</ref> <ref>PMID:1922338</ref> <ref>PMID:8879234</ref> <ref>PMID:9620674</ref> Allele B40:01: Presents immunodominant viral epitopes derived from EBV/HHV-4 LMP2 (IEDPPFNSL) and SARS-CoV-2 N/nucleoprotein (MEVTPSGTWL), triggering memory CD8-positive T cell response (PubMed:18991276, PubMed:32887977). Displays self-peptides sharing a signature motif, namely a Glu at position 2 and a Leu anchor residue at the C-terminus (PubMed:18991276).<ref>PMID:18991276</ref> <ref>PMID:32887977</ref> Allele B41:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B44:02: Presents immunodominant viral epitopes derived from EBV/HHV-4 EBNA4 (VEITPYKPTW) and EBNA6 (AEGGVGWRHW, EENLLDFVRF), triggering memory CD8-positive T cell response (PubMed:18991276, PubMed:9620674). Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Phe, Tyr or Trp anchor residues at the C-terminus (PubMed:18991276).<ref>PMID:18991276</ref> <ref>PMID:9620674</ref> Allele B45:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B46:01: Preferentially presents nonameric peptides sharing a signature motif, namely Ala and Leu at position 2 and Tyr, Phe, Leu, or Met anchor residues at the C-terminus. The peptide-bound form interacts with KIR2DL3 and inhibits NK cell cytotoxic response in a peptide-specific way.<ref>PMID:28514659</ref> Allele B47:01: Displays self-peptides sharing a signature motif, namely an Asp at position 2 and Leu or Met anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B49:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ile or Val anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B50:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B51:01: Presents an octomeric HIV-1 epitope derived from gag-pol (TAFTIPSI) to the public TRAV17/TRBV7-3 TCR clonotype, strongly suppressing HIV-1 replication.<ref>PMID:24600035</ref> Allele B54:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B55:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B56:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B57:01: The peptide-bound form recognizes KIR3DL1 and inhibits NK cell cytotoxic response. Presents HIV gag peptides (immunodominant KAFSPEVIPMF and subdominant KALGPAATL epitopes) predominantly to CD8-positive T cell clones expressing a TRAV41-containing TCR, triggering HLA-B-restricted T cell responses.<ref>PMID:22020283</ref> <ref>PMID:25480565</ref> <ref>PMID:34228645</ref> Allele B67:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Leu anchor residue at the C-terminus.<ref>PMID:7743181</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Altered protein phosphorylation in cancer cells often leads to surface presentation of phosphopeptide neoantigens. However, their role in cancer immunogenicity remains unclear. Here we describe a mechanism by which an HLA-B*0702-specific acute myeloid leukemia phosphoneoantigen, pMLL(747-755) (EPR(pS)PSHSM), is recognized by a cognate T cell receptor named TCR27, a candidate for cancer immunotherapy. We show that the replacement of phosphoserine P(4) with serine or phosphomimetics does not affect pMHC conformation or peptide-MHC affinity but abrogates TCR27-dependent T cell activation and weakens binding between TCR27 and pMHC. Here we describe the crystal structures for TCR27 and cognate pMHC, map of the interface produced by nuclear magnetic resonance, and a ternary complex generated using information-driven protein docking. Our data show that non-covalent interactions between the epitope phosphate group and TCR27 are crucial for TCR specificity. This study supports development of new treatment options for cancer patients through target expansion and TCR optimization.

			Molecular mechanism of phosphopeptide neoantigen immunogenicity.,Patskovsky Y, Natarajan A, Patskovska L, Nyovanie S, Joshi B, Morin B, Brittsan C, Huber O, Gordon S, Michelet X, Schmitzberger F, Stein RB, Findeis MA, Hurwitz A, Van Dijk M, Chantzoura E, Yague AS, Pollack Smith D, Buell JS, Underwood D, Krogsgaard M Nat Commun. 2023 Jun 23;14(1):3763. doi: 10.1038/s41467-023-39425-1. PMID:37353482<ref>PMID:37353482</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7s8a" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 18:10, 20 September 2023

2023-09-20T18:10:15Z

← Older revision		Revision as of 18:10, 20 September 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7s8a]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S8A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S8A FirstGlance]. <br>		<table><tr><td colspan='2'>[[7s8a]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S8A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S8A FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=12P:DODECAETHYLENE+GLYCOL'>12P</scene>, <scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=PE8:3,6,9,12,15,18,21-HEPTAOXATRICOSANE-1,23-DIOL'>PE8</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.1Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=12P:DODECAETHYLENE+GLYCOL'>12P</scene>, <scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=PE8:3,6,9,12,15,18,21-HEPTAOXATRICOSANE-1,23-DIOL'>PE8</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7s8a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s8a OCA], [https://pdbe.org/7s8a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s8a RCSB], [https://www.ebi.ac.uk/pdbsum/7s8a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s8a ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7s8a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s8a OCA], [https://pdbe.org/7s8a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s8a RCSB], [https://www.ebi.ac.uk/pdbsum/7s8a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s8a ProSAT]</span></td></tr>
	</table>		</table>
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/HLAB_HUMAN HLAB_HUMAN] Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-B-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:25808313, PubMed:29531227, PubMed:9620674, PubMed:23209413). May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usually inactivated to prevent autoreactivity (PubMed:7743181, PubMed:18991276). Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells (PubMed:29531227, PubMed:9620674, PubMed:24600035). Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via constitutive proteasome and IFNG-induced immunoproteasome (PubMed:23209413). Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9 (PubMed:25808313, PubMed:29531227).<ref>PMID:18991276</ref> <ref>PMID:23209413</ref> <ref>PMID:24600035</ref> <ref>PMID:25808313</ref> <ref>PMID:29531227</ref> <ref>PMID:7743181</ref> <ref>PMID:9620674</ref> Allele B07:02: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and mainly a Leu anchor residue at the C-terminus (PubMed:7743181). Presents a long peptide (APRGPHGGAASGL) derived from the cancer-testis antigen CTAG1A/NY-ESO-1, eliciting a polyclonal CD8-positive T cell response against tumor cells (PubMed:29531227). Presents viral epitopes derived from HIV-1 gag-pol (TPQDLNTML) and Nef (RPQVPLRPM) (PubMed:25808313). Presents an immunodominant epitope derived from SARS-CoV-2 N/nucleoprotein (SPRWYFYYL) (PubMed:32887977). Displays self-peptides including a peptide derived from the signal sequence of HLA-DPB1 (APRTVALTA) (PubMed:7743181).<ref>PMID:25808313</ref> <ref>PMID:29531227</ref> <ref>PMID:32887977</ref> <ref>PMID:7743181</ref> Allele B08:01: Presents to CD8-positive T cells viral epitopes derived from EBV/HHV-4 EBNA3 (QAKWRLQTL), eliciting cytotoxic T cell response.<ref>PMID:9620674</ref> Allele B13:02: Presents multiple HIV-1 epitopes derived from gag (RQANFLGKI, GQMREPRGSDI), nef (RQDILDLWI), gag-pol (RQYDQILIE, GQGQWTYQI) and rev (LQLPPLERL), all having in common a Gln residue at position 2 and mainly hydrophobic amino acids Leu, Ile or Val at the C-terminus. Associated with succesful control of HIV-1 infection.<ref>PMID:17251285</ref> Allele B18:01: Preferentially presents octomeric and nonameric peptides sharing a common motif, namely a Glu at position 2 and Phe or Tyr anchor residues at the C-terminus (PubMed:14978097, PubMed:23749632, PubMed:18991276). Presents an EBV/HHV-4 epitope derived from BZLF1 (SELEIKRY) (PubMed:23749632). May present to CD8-positive T cells an antigenic peptide derived from MAGEA3 (MEVDPIGHLY), triggering an anti-tumor immune response (PubMed:12366779). May display a broad repertoire of self-peptides with a preference for peptides derived from RNA-binding proteins (PubMed:14978097).<ref>PMID:12366779</ref> <ref>PMID:14978097</ref> <ref>PMID:18991276</ref> <ref>PMID:23749632</ref> Allele B27:05: Presents to CD8-positive T cells immunodominant viral epitopes derived from HCV POLG (ARMILMTHF), HIV-1 gag (KRWIILGLNK), IAV NP (SRYWAIRTR), SARS-CoV-2 N/nucleoprotein (QRNAPRITF), EBV/HHV-4 EBNA4 (HRCQAIRKK) and EBV/HHV-4 EBNA6 (RRIYDLIEL), confering longterm protection against viral infection (PubMed:19139562, PubMed:18385228, PubMed:15113903, PubMed:9620674, PubMed:32887977). Can present self-peptides derived from cytosolic and nuclear proteins. All peptides carry an Arg at position 2 (PubMed:1922338). The peptide-bound form interacts with NK cell inhibitory receptor KIR3DL1 and inhibits NK cell activation in a peptide-specific way, being particularly sensitive to the nature of the amino acid side chain at position 8 of the antigenic peptide (PubMed:8879234, PubMed:15657948). KIR3DL1 fails to recognize HLA-B27:05 in complex with B2M and EBV/HHV-4 EBNA6 (RRIYDLIEL) peptide, which can lead to increased activation of NK cells during infection (PubMed:15657948). May present an altered repertoire of peptides in the absence of TAP1-TAP2 and TAPBPL (PubMed:9620674).<ref>PMID:15113903</ref> <ref>PMID:15657948</ref> <ref>PMID:18385228</ref> <ref>PMID:19139562</ref> <ref>PMID:1922338</ref> <ref>PMID:8879234</ref> <ref>PMID:9620674</ref> Allele B40:01: Presents immunodominant viral epitopes derived from EBV/HHV-4 LMP2 (IEDPPFNSL) and SARS-CoV-2 N/nucleoprotein (MEVTPSGTWL), triggering memory CD8-positive T cell response (PubMed:18991276, PubMed:32887977). Displays self-peptides sharing a signature motif, namely a Glu at position 2 and a Leu anchor residue at the C-terminus (PubMed:18991276).<ref>PMID:18991276</ref> <ref>PMID:32887977</ref> Allele B41:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B44:02: Presents immunodominant viral epitopes derived from EBV/HHV-4 EBNA4 (VEITPYKPTW) and EBNA6 (AEGGVGWRHW, EENLLDFVRF), triggering memory CD8-positive T cell response (PubMed:9620674, PubMed:18991276). Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Phe, Tyr or Trp anchor residues at the C-terminus (PubMed:18991276).<ref>PMID:18991276</ref> <ref>PMID:9620674</ref> Allele B45:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B46:01: Preferentially presents nonameric peptides sharing a signature motif, namely Ala and Leu at position 2 and Tyr, Phe, Leu, or Met anchor residues at the C-terminus. The peptide-bound form interacts with KIR2DL3 and inhibits NK cell cytotoxic response in a peptide-specific way.<ref>PMID:28514659</ref> Allele B47:01: Displays self-peptides sharing a signature motif, namely an Asp at position 2 and Leu or Met anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B49:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ile or Val anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B50:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B51:01: Presents an octomeric HIV-1 epitope derived from gag-pol (TAFTIPSI) to the public TRAV17/TRBV7-3 TCR clonotype, strongly suppressing HIV-1 replication.<ref>PMID:24600035</ref> Allele B54:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B55:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B56:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B57:01: The peptide-bound form recognizes KIR3DL1 and inhibits NK cell cytotoxic response.<ref>PMID:22020283</ref> <ref>PMID:25480565</ref> Allele B67:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Leu anchor residue at the C-terminus.<ref>PMID:7743181</ref>		[https://www.uniprot.org/uniprot/HLAB_HUMAN HLAB_HUMAN] Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-B-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:25808313, PubMed:29531227, PubMed:9620674, PubMed:23209413). May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usually inactivated to prevent autoreactivity (PubMed:7743181, PubMed:18991276). Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells (PubMed:29531227, PubMed:9620674, PubMed:24600035). Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via constitutive proteasome and IFNG-induced immunoproteasome (PubMed:23209413). Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9 (PubMed:25808313, PubMed:29531227).<ref>PMID:18991276</ref> <ref>PMID:23209413</ref> <ref>PMID:24600035</ref> <ref>PMID:25808313</ref> <ref>PMID:29531227</ref> <ref>PMID:7743181</ref> <ref>PMID:9620674</ref> Allele B07:02: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and mainly a Leu anchor residue at the C-terminus (PubMed:7743181). Presents a long peptide (APRGPHGGAASGL) derived from the cancer-testis antigen CTAG1A/NY-ESO-1, eliciting a polyclonal CD8-positive T cell response against tumor cells (PubMed:29531227). Presents viral epitopes derived from HIV-1 gag-pol (TPQDLNTML) and Nef (RPQVPLRPM) (PubMed:25808313). Presents an immunodominant epitope derived from SARS-CoV-2 N/nucleoprotein (SPRWYFYYL) (PubMed:32887977). Displays self-peptides including a peptide derived from the signal sequence of HLA-DPB1 (APRTVALTA) (PubMed:7743181).<ref>PMID:25808313</ref> <ref>PMID:29531227</ref> <ref>PMID:32887977</ref> <ref>PMID:7743181</ref> Allele B08:01: Presents to CD8-positive T cells viral epitopes derived from EBV/HHV-4 EBNA3 (QAKWRLQTL), eliciting cytotoxic T cell response.<ref>PMID:9620674</ref> Allele B13:02: Presents multiple HIV-1 epitopes derived from gag (RQANFLGKI, GQMREPRGSDI), nef (RQDILDLWI), gag-pol (RQYDQILIE, GQGQWTYQI) and rev (LQLPPLERL), all having in common a Gln residue at position 2 and mainly hydrophobic amino acids Leu, Ile or Val at the C-terminus. Associated with succesful control of HIV-1 infection.<ref>PMID:17251285</ref> Allele B18:01: Preferentially presents octomeric and nonameric peptides sharing a common motif, namely a Glu at position 2 and Phe or Tyr anchor residues at the C-terminus (PubMed:14978097, PubMed:23749632, PubMed:18991276). Presents an EBV/HHV-4 epitope derived from BZLF1 (SELEIKRY) (PubMed:23749632). May present to CD8-positive T cells an antigenic peptide derived from MAGEA3 (MEVDPIGHLY), triggering an anti-tumor immune response (PubMed:12366779). May display a broad repertoire of self-peptides with a preference for peptides derived from RNA-binding proteins (PubMed:14978097).<ref>PMID:12366779</ref> <ref>PMID:14978097</ref> <ref>PMID:18991276</ref> <ref>PMID:23749632</ref> Allele B27:05: Presents to CD8-positive T cells immunodominant viral epitopes derived from HCV POLG (ARMILMTHF), HIV-1 gag (KRWIILGLNK), IAV NP (SRYWAIRTR), SARS-CoV-2 N/nucleoprotein (QRNAPRITF), EBV/HHV-4 EBNA4 (HRCQAIRKK) and EBV/HHV-4 EBNA6 (RRIYDLIEL), confering longterm protection against viral infection (PubMed:19139562, PubMed:18385228, PubMed:15113903, PubMed:9620674, PubMed:32887977). Can present self-peptides derived from cytosolic and nuclear proteins. All peptides carry an Arg at position 2 (PubMed:1922338). The peptide-bound form interacts with NK cell inhibitory receptor KIR3DL1 and inhibits NK cell activation in a peptide-specific way, being particularly sensitive to the nature of the amino acid side chain at position 8 of the antigenic peptide (PubMed:8879234, PubMed:15657948). KIR3DL1 fails to recognize HLA-B27:05 in complex with B2M and EBV/HHV-4 EBNA6 (RRIYDLIEL) peptide, which can lead to increased activation of NK cells during infection (PubMed:15657948). May present an altered repertoire of peptides in the absence of TAP1-TAP2 and TAPBPL (PubMed:9620674).<ref>PMID:15113903</ref> <ref>PMID:15657948</ref> <ref>PMID:18385228</ref> <ref>PMID:19139562</ref> <ref>PMID:1922338</ref> <ref>PMID:8879234</ref> <ref>PMID:9620674</ref> Allele B40:01: Presents immunodominant viral epitopes derived from EBV/HHV-4 LMP2 (IEDPPFNSL) and SARS-CoV-2 N/nucleoprotein (MEVTPSGTWL), triggering memory CD8-positive T cell response (PubMed:18991276, PubMed:32887977). Displays self-peptides sharing a signature motif, namely a Glu at position 2 and a Leu anchor residue at the C-terminus (PubMed:18991276).<ref>PMID:18991276</ref> <ref>PMID:32887977</ref> Allele B41:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B44:02: Presents immunodominant viral epitopes derived from EBV/HHV-4 EBNA4 (VEITPYKPTW) and EBNA6 (AEGGVGWRHW, EENLLDFVRF), triggering memory CD8-positive T cell response (PubMed:9620674, PubMed:18991276). Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Phe, Tyr or Trp anchor residues at the C-terminus (PubMed:18991276).<ref>PMID:18991276</ref> <ref>PMID:9620674</ref> Allele B45:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B46:01: Preferentially presents nonameric peptides sharing a signature motif, namely Ala and Leu at position 2 and Tyr, Phe, Leu, or Met anchor residues at the C-terminus. The peptide-bound form interacts with KIR2DL3 and inhibits NK cell cytotoxic response in a peptide-specific way.<ref>PMID:28514659</ref> Allele B47:01: Displays self-peptides sharing a signature motif, namely an Asp at position 2 and Leu or Met anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B49:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ile or Val anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B50:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B51:01: Presents an octomeric HIV-1 epitope derived from gag-pol (TAFTIPSI) to the public TRAV17/TRBV7-3 TCR clonotype, strongly suppressing HIV-1 replication.<ref>PMID:24600035</ref> Allele B54:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B55:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B56:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B57:01: The peptide-bound form recognizes KIR3DL1 and inhibits NK cell cytotoxic response.<ref>PMID:22020283</ref> <ref>PMID:25480565</ref> Allele B67:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Leu anchor residue at the C-terminus.<ref>PMID:7743181</ref>

			==See Also==
			*[[MHC 3D structures\|MHC 3D structures]]
			*[[MHC I 3D structures\|MHC I 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 07:14, 3 November 2022

2022-11-03T07:14:11Z

← Older revision		Revision as of 07:14, 3 November 2022
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	~~'''Unreleased structure'''~~

	~~The entry~~ 7s8a is ~~ON HOLD until Paper Publication~~		==STRUCTURE OF HLA-B*07:02 IN COMPLEX WITH MLL(747-755) PHOSPHOPEPTIDE, CUBIC CRYSTAL FORM==
			<StructureSection load='7s8a' size='340' side='right'caption='[[7s8a]], [[Resolution\|resolution]] 2.10Å' scene=''>
	~~Authors~~: ~~Patskovska~~, L., ~~Patskovsky~~, Y., ~~Nyovanie~~, S., ~~Natarajan~~, A., ~~Joshi~~, B., ~~Morin~~, B., ~~Brittsan~~, C., ~~Huber~~, O., ~~Gordon~~, S., ~~Michelet~~, X., ~~Schmitzberger~~, F., ~~Stein~~, R., ~~Findeis~~, M., ~~Hurwitz~~, A., ~~Van Dijk~~, M., ~~Buell~~, J., ~~Underwood~~, D., ~~Krogsgaard~~, M.		== Structural highlights ==
			<table><tr><td colspan='2'>[[7s8a]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7S8A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7S8A FirstGlance]. <br>
	~~Description~~: ~~STRUCTURE OF HLA~~-B*07:~~02 IN COMPLEX WITH MLL(747~~-~~755) PHOSPHOPEPTIDE~~, ~~CUBIC CRYSTAL FORM~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=12P:DODECAETHYLENE+GLYCOL'>12P</scene>, <scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=PE8:3,6,9,12,15,18,21-HEPTAOXATRICOSANE-1,23-DIOL'>PE8</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
	[[Category: ~~Unreleased Structures~~]]		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7s8a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7s8a OCA], [https://pdbe.org/7s8a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7s8a RCSB], [https://www.ebi.ac.uk/pdbsum/7s8a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7s8a ProSAT]</span></td></tr>
	[[Category: ~~Natarajan, A~~]]		</table>
	[[Category: ~~Michelet, X~~]]		== Disease ==
	[[Category: ~~Morin, B~~]]		[https://www.uniprot.org/uniprot/HLAB_HUMAN HLAB_HUMAN] Prediction of allopurinol toxicity;NON RARE IN EUROPE: Ankylosing spondylitis;Prediction of flucloxacilline toxicity;Giant cell arteritis;Takayasu arteritis;Reactive arthritis;Behcet disease;Stevens-Johnson syndrome;Prediction of phenytoin or carbamazepine toxicity;Pulmonary arterial hypertension associated with connective tissue disease;Prediction of abacavir toxicity. Disease susceptibility is associated with variants affecting the gene represented in this entry. Increased susceptibility to Stevens-Johnson syndrome is conferred by allele B15:02.<ref>PMID:15057820</ref> Disease susceptibility is associated with variants affecting the gene represented in this entry. A restricted number of HLA-B27 subtypes can be associated with ankylosing spondylitis and other B27-related diseases, and an elevated frequency of the B27:02 allele in ankylosing spondylitis patients is identified. The allele B27:07 seems to have a protective role in some populations because it was found only in the healthy controls.<ref>PMID:15603872</ref> There is evidence that HLA-B51 is associated with susceptibility to Behcet disease (BD). However, it is not certain whether HLA-B51 itself or a closely linked gene is responsible for susceptibility. The world distribution of HLA-B51 in healthy people corresponds to the global distribution of BD; in Southern hemisphere countries (Africa, South Pacific, etc.) and in some parts of Europe, the prevalence of HLA-B51 in healthy people is low or null, corresponding to a low prevalence of BD. The wide variation that exists in the relative risk of HLA-B51 would support other nongenetic risk factors.<ref>PMID:23291587</ref> The presence of allele B57:01 is associated with increased susceptibility to abacavir hypersensitivity [MIM:[https://omim.org/entry/142830 142830] in HIV-1 patients.<ref>PMID:11888582</ref> Allele group B08 is associated with increased susceptibility to rheumatoid arthritis, where affected individuals have antibodies to cyclic citrullinated peptide (anti-CCP-positive rheumatoid arthritis).<ref>PMID:22286218</ref>
	[[Category: ~~Brittsan, C~~]]		== Function ==
	[[Category: ~~Krogsgaard, M~~]]		[https://www.uniprot.org/uniprot/HLAB_HUMAN HLAB_HUMAN] Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-B-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:25808313, PubMed:29531227, PubMed:9620674, PubMed:23209413). May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usually inactivated to prevent autoreactivity (PubMed:7743181, PubMed:18991276). Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells (PubMed:29531227, PubMed:9620674, PubMed:24600035). Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via constitutive proteasome and IFNG-induced immunoproteasome (PubMed:23209413). Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9 (PubMed:25808313, PubMed:29531227).<ref>PMID:18991276</ref> <ref>PMID:23209413</ref> <ref>PMID:24600035</ref> <ref>PMID:25808313</ref> <ref>PMID:29531227</ref> <ref>PMID:7743181</ref> <ref>PMID:9620674</ref> Allele B07:02: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and mainly a Leu anchor residue at the C-terminus (PubMed:7743181). Presents a long peptide (APRGPHGGAASGL) derived from the cancer-testis antigen CTAG1A/NY-ESO-1, eliciting a polyclonal CD8-positive T cell response against tumor cells (PubMed:29531227). Presents viral epitopes derived from HIV-1 gag-pol (TPQDLNTML) and Nef (RPQVPLRPM) (PubMed:25808313). Presents an immunodominant epitope derived from SARS-CoV-2 N/nucleoprotein (SPRWYFYYL) (PubMed:32887977). Displays self-peptides including a peptide derived from the signal sequence of HLA-DPB1 (APRTVALTA) (PubMed:7743181).<ref>PMID:25808313</ref> <ref>PMID:29531227</ref> <ref>PMID:32887977</ref> <ref>PMID:7743181</ref> Allele B08:01: Presents to CD8-positive T cells viral epitopes derived from EBV/HHV-4 EBNA3 (QAKWRLQTL), eliciting cytotoxic T cell response.<ref>PMID:9620674</ref> Allele B13:02: Presents multiple HIV-1 epitopes derived from gag (RQANFLGKI, GQMREPRGSDI), nef (RQDILDLWI), gag-pol (RQYDQILIE, GQGQWTYQI) and rev (LQLPPLERL), all having in common a Gln residue at position 2 and mainly hydrophobic amino acids Leu, Ile or Val at the C-terminus. Associated with succesful control of HIV-1 infection.<ref>PMID:17251285</ref> Allele B18:01: Preferentially presents octomeric and nonameric peptides sharing a common motif, namely a Glu at position 2 and Phe or Tyr anchor residues at the C-terminus (PubMed:14978097, PubMed:23749632, PubMed:18991276). Presents an EBV/HHV-4 epitope derived from BZLF1 (SELEIKRY) (PubMed:23749632). May present to CD8-positive T cells an antigenic peptide derived from MAGEA3 (MEVDPIGHLY), triggering an anti-tumor immune response (PubMed:12366779). May display a broad repertoire of self-peptides with a preference for peptides derived from RNA-binding proteins (PubMed:14978097).<ref>PMID:12366779</ref> <ref>PMID:14978097</ref> <ref>PMID:18991276</ref> <ref>PMID:23749632</ref> Allele B27:05: Presents to CD8-positive T cells immunodominant viral epitopes derived from HCV POLG (ARMILMTHF), HIV-1 gag (KRWIILGLNK), IAV NP (SRYWAIRTR), SARS-CoV-2 N/nucleoprotein (QRNAPRITF), EBV/HHV-4 EBNA4 (HRCQAIRKK) and EBV/HHV-4 EBNA6 (RRIYDLIEL), confering longterm protection against viral infection (PubMed:19139562, PubMed:18385228, PubMed:15113903, PubMed:9620674, PubMed:32887977). Can present self-peptides derived from cytosolic and nuclear proteins. All peptides carry an Arg at position 2 (PubMed:1922338). The peptide-bound form interacts with NK cell inhibitory receptor KIR3DL1 and inhibits NK cell activation in a peptide-specific way, being particularly sensitive to the nature of the amino acid side chain at position 8 of the antigenic peptide (PubMed:8879234, PubMed:15657948). KIR3DL1 fails to recognize HLA-B27:05 in complex with B2M and EBV/HHV-4 EBNA6 (RRIYDLIEL) peptide, which can lead to increased activation of NK cells during infection (PubMed:15657948). May present an altered repertoire of peptides in the absence of TAP1-TAP2 and TAPBPL (PubMed:9620674).<ref>PMID:15113903</ref> <ref>PMID:15657948</ref> <ref>PMID:18385228</ref> <ref>PMID:19139562</ref> <ref>PMID:1922338</ref> <ref>PMID:8879234</ref> <ref>PMID:9620674</ref> Allele B40:01: Presents immunodominant viral epitopes derived from EBV/HHV-4 LMP2 (IEDPPFNSL) and SARS-CoV-2 N/nucleoprotein (MEVTPSGTWL), triggering memory CD8-positive T cell response (PubMed:18991276, PubMed:32887977). Displays self-peptides sharing a signature motif, namely a Glu at position 2 and a Leu anchor residue at the C-terminus (PubMed:18991276).<ref>PMID:18991276</ref> <ref>PMID:32887977</ref> Allele B41:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B44:02: Presents immunodominant viral epitopes derived from EBV/HHV-4 EBNA4 (VEITPYKPTW) and EBNA6 (AEGGVGWRHW, EENLLDFVRF), triggering memory CD8-positive T cell response (PubMed:9620674, PubMed:18991276). Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Phe, Tyr or Trp anchor residues at the C-terminus (PubMed:18991276).<ref>PMID:18991276</ref> <ref>PMID:9620674</ref> Allele B45:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B46:01: Preferentially presents nonameric peptides sharing a signature motif, namely Ala and Leu at position 2 and Tyr, Phe, Leu, or Met anchor residues at the C-terminus. The peptide-bound form interacts with KIR2DL3 and inhibits NK cell cytotoxic response in a peptide-specific way.<ref>PMID:28514659</ref> Allele B47:01: Displays self-peptides sharing a signature motif, namely an Asp at position 2 and Leu or Met anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B49:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ile or Val anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B50:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.<ref>PMID:18991276</ref> Allele B51:01: Presents an octomeric HIV-1 epitope derived from gag-pol (TAFTIPSI) to the public TRAV17/TRBV7-3 TCR clonotype, strongly suppressing HIV-1 replication.<ref>PMID:24600035</ref> Allele B54:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B55:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B56:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.<ref>PMID:7743181</ref> Allele B57:01: The peptide-bound form recognizes KIR3DL1 and inhibits NK cell cytotoxic response.<ref>PMID:22020283</ref> <ref>PMID:25480565</ref> Allele B67:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Leu anchor residue at the C-terminus.<ref>PMID:7743181</ref>
	[[Category: ~~Patskovska, L~~]]		== References ==
	[[Category: ~~Buell, J~~]]		<references/>
	[[Category: Joshi, B]]		__TOC__
	[[Category: ~~Schmitzberger, F~~]]		</StructureSection>
	[[Category: ~~Van Dijk, M~~]]		[[Category: Homo sapiens]]
	[[Category: ~~Gordon, S~~]]		[[Category: Large Structures]]
	[[Category: ~~Stein, R~~]]		[[Category: Brittsan C]]
	[[Category: Nyovanie, S]]		[[Category: Buell J]]
	[[Category: ~~Underwood, D~~]]		[[Category: Findeis M]]
	[[Category: ~~Hurwitz, A~~]]		[[Category: Gordon S]]
	[[Category: ~~Patskovsky, Y~~]]		[[Category: Huber O]]
	[[Category: ~~Findeis, M~~]]		[[Category: Hurwitz A]]
	[[Category: ~~Huber, O~~]]		[[Category: Joshi B]]
			[[Category: Krogsgaard M]]
			[[Category: Michelet X]]
			[[Category: Morin B]]
			[[Category: Natarajan A]]
			[[Category: Nyovanie S]]
			[[Category: Patskovska L]]
			[[Category: Patskovsky Y]]
			[[Category: Schmitzberger F]]
			[[Category: Stein R]]
			[[Category: Underwood D]]
			[[Category: Van Dijk M]]

OCA at 12:39, 27 October 2021

2021-10-27T12:39:56Z

← Older revision		Revision as of 12:39, 27 October 2021
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	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7s8a is ON HOLD		The entry 7s8a is ON HOLD until Paper Publication

	Authors: Patskovska, L., Patskovsky, Y., Nyovanie, S., Natarajan, A., Joshi, B., Morin, B., Brittsan, C., Huber, O., Gordon, S., Michelet, X., Schmitzberger, F., Stein, R., Findeis, M., Hurwitz, A., Van Dijk, M., Buell, J., Underwood, D., Krogsgaard, M.		Authors: Patskovska, L., Patskovsky, Y., Nyovanie, S., Natarajan, A., Joshi, B., Morin, B., Brittsan, C., Huber, O., Gordon, S., Michelet, X., Schmitzberger, F., Stein, R., Findeis, M., Hurwitz, A., Van Dijk, M., Buell, J., Underwood, D., Krogsgaard, M.
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	Description: STRUCTURE OF HLA-B*07:02 IN COMPLEX WITH MLL(747-755) PHOSPHOPEPTIDE, CUBIC CRYSTAL FORM		Description: STRUCTURE OF HLA-B*07:02 IN COMPLEX WITH MLL(747-755) PHOSPHOPEPTIDE, CUBIC CRYSTAL FORM
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
			[[Category: Natarajan, A]]
			[[Category: Michelet, X]]
	[[Category: Morin, B]]		[[Category: Morin, B]]
	[[Category: Brittsan, C]]		[[Category: Brittsan, C]]
			[[Category: Krogsgaard, M]]
			[[Category: Patskovska, L]]
			[[Category: Buell, J]]
			[[Category: Joshi, B]]
	[[Category: Schmitzberger, F]]		[[Category: Schmitzberger, F]]
	[[Category: Van Dijk, M]]		[[Category: Van Dijk, M]]
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	[[Category: Stein, R]]		[[Category: Stein, R]]
	[[Category: Nyovanie, S]]		[[Category: Nyovanie, S]]
			[[Category: Underwood, D]]
	[[Category: Hurwitz, A]]		[[Category: Hurwitz, A]]
	[[Category: Patskovsky, Y]]		[[Category: Patskovsky, Y]]
			[[Category: Findeis, M]]
	[[Category: Huber, O]]		[[Category: Huber, O]]
	~~[[Category: Natarajan, A]]~~
	~~[[Category: Michelet, X]]~~
	~~[[Category: Krogsgaard, M]]~~
	~~[[Category: Patskovska, L]]~~
	~~[[Category: Buell, J]]~~
	~~[[Category: Joshi, B]]~~
	~~[[Category: Underwood, D]]~~
	~~[[Category: Findeis, M]]~~

OCA: Protected "7s8a" [edit=sysop:move=sysop]

2021-09-29T07:46:33Z

Protected "7s8a" [edit=sysop:move=sysop]

← Older revision	Revision as of 07:46, 29 September 2021
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7s8a is ON HOLD Authors: Patskovska, L., Patskovsky, Y., Nyovanie, S., Natarajan, A., Joshi, B., Morin, B., Brittsan, C., Huber, O., Gordon, S., Mic...

2021-09-29T07:46:31Z

New page: '''Unreleased structure''' The entry 7s8a is ON HOLD Authors: Patskovska, L., Patskovsky, Y., Nyovanie, S., Natarajan, A., Joshi, B., Morin, B., Brittsan, C., Huber, O., Gordon, S., Mic...

New page

'''Unreleased structure'''

The entry 7s8a is ON HOLD

Authors: Patskovska, L., Patskovsky, Y., Nyovanie, S., Natarajan, A., Joshi, B., Morin, B., Brittsan, C., Huber, O., Gordon, S., Michelet, X., Schmitzberger, F., Stein, R., Findeis, M., Hurwitz, A., Van Dijk, M., Buell, J., Underwood, D., Krogsgaard, M.

Description: STRUCTURE OF HLA-B*07:02 IN COMPLEX WITH MLL(747-755) PHOSPHOPEPTIDE, CUBIC CRYSTAL FORM
[[Category: Unreleased Structures]]
[[Category: Morin, B]]
[[Category: Brittsan, C]]
[[Category: Schmitzberger, F]]
[[Category: Van Dijk, M]]
[[Category: Gordon, S]]
[[Category: Stein, R]]
[[Category: Nyovanie, S]]
[[Category: Hurwitz, A]]
[[Category: Patskovsky, Y]]
[[Category: Huber, O]]
[[Category: Natarajan, A]]
[[Category: Michelet, X]]
[[Category: Krogsgaard, M]]
[[Category: Patskovska, L]]
[[Category: Buell, J]]
[[Category: Joshi, B]]
[[Category: Underwood, D]]
[[Category: Findeis, M]]