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

Richard W Birkinshaw, Daniel G Pellicci, Tan-Yun Cheng, Andrew N Keller, Maria L Sandoval-Romero, Stephanie Gras, Annemieke de Jong, Adam P Uldrich, D Branch Moody, Dale I Godfrey, Jamie Rossjohn

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77 Citations (Scopus)

Abstract

A central paradigm in alphabeta T cell-mediated immunity is the simultaneous co-recognition of antigens and antigen-presenting molecules by the alphabeta 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 alphabeta T cells indirectly sense self antigens that are bound to an antigen-presenting molecule.
Original languageEnglish
Pages (from-to)258-266
Number of pages9
JournalNature Immunology
Volume16
Issue number3
DOIs
Publication statusPublished - 2015

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