αβ T cell antigen receptor recognition of CD1a presenting self lipid ligands

Birkinshaw, Richard W., Pellicci, Daniel G., Cheng, Tan-Yun, Keller, Andrew N., Sandoval-Romero, Maria, Gras, Stephanie, de Jong, Annemieke, Uldrich, Adam P., Moody, D. Branch, Godfrey, Dale I. and Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522 2015. αβ T cell antigen receptor recognition of CD1a presenting self lipid ligands. Nature Immunology 16 , pp. 258-266. 10.1038/ni.3098

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Abstract

A central paradigm in αβ T cell–mediated immunity is the simultaneous co-recognition of antigens and antigen-presenting molecules by the αβ T cell antigen receptor (TCR). CD1a presents a broad repertoire of lipid-based antigens. We found that a prototypical autoreactive TCR bound CD1a when it was presenting a series of permissive endogenous ligands, while other lipid ligands were nonpermissive to TCR binding. The structures of two TCR-CD1a-lipid complexes showed that the TCR docked over the A′ roof of CD1a in a manner that precluded direct contact with permissive ligands. Nonpermissive ligands indirectly inhibited TCR binding by disrupting the TCR-CD1a contact zone. The exclusive recognition of CD1a by the TCR represents a previously unknown mechanism whereby αβ T cells indirectly sense self antigens that are bound to an antigen-presenting molecule.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	Nature Publishing Group
ISSN:	1529-2908
Date of Acceptance:	6 January 2015
Last Modified:	31 Oct 2022 10:25
URI:	https://orca.cardiff.ac.uk/id/eprint/84816

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