| Structural highlights
Function
CD1C_HUMAN Antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells.[1] [2] [3] [4] CD1B_HUMAN Antigen-presenting protein that binds self and non-self lipid and glycolipid antigens and presents them to T-cell receptors on natural killer T-cells.[5] [6]
Publication Abstract from PubMed
Cluster of differentiation 1c (CD1c)-dependent self-reactive T cells are abundant in human blood, but self-antigens presented by CD1c to the T-cell receptors of these cells are poorly understood. Here we present a crystal structure of CD1c determined at 2.4 A revealing an extended ligand binding potential of the antigen groove and a substantially different conformation compared with known CD1c structures. Computational simulations exploring different occupancy states of the groove reenacted these different CD1c conformations and suggested cholesteryl esters (CE) and acylated steryl glycosides (ASG) as new ligand classes for CD1c. Confirming this, we show that binding of CE and ASG to CD1c enables the binding of human CD1c self-reactive T-cell receptors. Hence, human CD1c adopts different conformations dependent on ligand occupancy of its groove, with CE and ASG stabilizing CD1c conformations that provide a footprint for binding of CD1c self-reactive T-cell receptors.
Cholesteryl esters stabilize human CD1c conformations for recognition by self-reactive T cells.,Mansour S, Tocheva AS, Cave-Ayland C, Machelett MM, Sander B, Lissin NM, Molloy PE, Baird MS, Stubs G, Schroder NW, Schumann RR, Rademann J, Postle AD, Jakobsen BK, Marshall BG, Gosain R, Elkington PT, Elliott T, Skylaris CK, Essex JW, Tews I, Gadola SD Proc Natl Acad Sci U S A. 2016 Feb 16. pii: 201519246. PMID:26884207[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Moody DB, Ulrichs T, Muhlecker W, Young DC, Gurcha SS, Grant E, Rosat JP, Brenner MB, Costello CE, Besra GS, Porcelli SA. CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection. Nature. 2000 Apr 20;404(6780):884-8. PMID:10786796 doi:http://dx.doi.org/10.1038/35009119
- ↑ Sugita M, van Der Wel N, Rogers RA, Peters PJ, Brenner MB. CD1c molecules broadly survey the endocytic system. Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8445-50. PMID:10890914 doi:http://dx.doi.org/10.1073/pnas.150236797
- ↑ Briken V, Jackman RM, Watts GF, Rogers RA, Porcelli SA. Human CD1b and CD1c isoforms survey different intracellular compartments for the presentation of microbial lipid antigens. J Exp Med. 2000 Jul 17;192(2):281-8. PMID:10899914
- ↑ Scharf L, Li NS, Hawk AJ, Garzon D, Zhang T, Fox LM, Kazen AR, Shah S, Haddadian EJ, Gumperz JE, Saghatelian A, Faraldo-Gomez JD, Meredith SC, Piccirilli JA, Adams EJ. The 2.5 a structure of CD1c in complex with a mycobacterial lipid reveals an open groove ideally suited for diverse antigen presentation. Immunity. 2010 Dec 14;33(6):853-62. PMID:21167756 doi:10.1016/j.immuni.2010.11.026
- ↑ Shamshiev A, Donda A, Prigozy TI, Mori L, Chigorno V, Benedict CA, Kappos L, Sonnino S, Kronenberg M, De Libero G. The alphabeta T cell response to self-glycolipids shows a novel mechanism of CD1b loading and a requirement for complex oligosaccharides. Immunity. 2000 Aug;13(2):255-64. PMID:10981968
- ↑ Winau F, Schwierzeck V, Hurwitz R, Remmel N, Sieling PA, Modlin RL, Porcelli SA, Brinkmann V, Sugita M, Sandhoff K, Kaufmann SH, Schaible UE. Saposin C is required for lipid presentation by human CD1b. Nat Immunol. 2004 Feb;5(2):169-74. Epub 2004 Jan 11. PMID:14716313 doi:10.1038/ni1035
- ↑ Mansour S, Tocheva AS, Cave-Ayland C, Machelett MM, Sander B, Lissin NM, Molloy PE, Baird MS, Stubs G, Schroder NW, Schumann RR, Rademann J, Postle AD, Jakobsen BK, Marshall BG, Gosain R, Elkington PT, Elliott T, Skylaris CK, Essex JW, Tews I, Gadola SD. Cholesteryl esters stabilize human CD1c conformations for recognition by self-reactive T cells. Proc Natl Acad Sci U S A. 2016 Feb 16. pii: 201519246. PMID:26884207 doi:http://dx.doi.org/10.1073/pnas.1519246113
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