6C09

Ternary crystal structure of the 3C8 TCR-CD1c-monoacylglycerol complex

Summary for 6C09

• Entry DOI: 10.2210/pdb6c09/pdb
• Descriptor: T-cell surface glycoprotein CD1c, DI(HYDROXYETHYL)ETHER, Beta-2-microglobulin, ... (11 entities in total)
• Functional Keywords: t cell receptor, antigen presentation, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 96710.37

Authors

Wun, K.S.,Rossjohn, J. (deposition date: 2017-12-28, release date: 2018-03-21, Last modification date: 2024-11-13)

Primary citation

Wun, K.S.,Reijneveld, J.F.,Cheng, T.Y.,Ladell, K.,Uldrich, A.P.,Le Nours, J.,Miners, K.L.,McLaren, J.E.,Grant, E.J.,Haigh, O.L.,Watkins, T.S.,Suliman, S.,Iwany, S.,Jimenez, J.,Calderon, R.,Tamara, K.L.,Leon, S.R.,Murray, M.B.,Mayfield, J.A.,Altman, J.D.,Purcell, A.W.,Miles, J.J.,Godfrey, D.I.,Gras, S.,Price, D.A.,Van Rhijn, I.,Moody, D.B.,Rossjohn, J.
T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids.
Nat. Immunol., 19:397-406, 2018

PubMed Abstract: The hallmark function of αβ 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.

PubMed: 29531339
DOI: 10.1038/s41590-018-0065-7

Experimental method

X-RAY DIFFRACTION (2.95 Å)