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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 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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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: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Nature Publishing Group
ISSN: 1529-2908
Date of Acceptance: 6 January 2015
Last Modified: 20 Jan 2021 11:00

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