6c09
From Proteopedia
Ternary crystal structure of the 3C8 TCR-CD1c-monoacylglycerol complex
Structural highlights
FunctionCD1C_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] Publication Abstract from PubMedThe hallmark function of alphabeta T cell antigen receptors (TCRs) involves the highly specific co-recognition of a major histocompatibility complex molecule and its carried peptide. However, the molecular basis of the interactions of TCRs with the lipid antigen-presenting molecule CD1c is unknown. We identified frequent staining of human T cells with CD1c tetramers across numerous subjects. Whereas TCRs typically show high specificity for antigen, both tetramer binding and autoreactivity occurred with CD1c in complex with numerous, chemically diverse self lipids. Such extreme polyspecificity was attributable to binding of the TCR over the closed surface of CD1c, with the TCR covering the portal where lipids normally protrude. The TCR essentially failed to contact lipids because they were fully seated within CD1c. These data demonstrate the sequestration of lipids within CD1c as a mechanism of autoreactivity and point to small lipid size as a determinant of autoreactive T cell responses. T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids.,Wun KS, Reijneveld JF, Cheng TY, Ladell K, Uldrich AP, Le Nours J, Miners KL, McLaren JE, Grant EJ, Haigh OL, Watkins TS, Suliman S, Iwany S, Jimenez J, Calderon R, Tamara KL, Leon SR, Murray MB, Mayfield JA, Altman JD, Purcell AW, Miles JJ, Godfrey DI, Gras S, Price DA, Van Rhijn I, Moody DB, Rossjohn J Nat Immunol. 2018 Apr;19(4):397-406. doi: 10.1038/s41590-018-0065-7. Epub 2018, Mar 12. PMID:29531339[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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