alpha beta T cell antigen receptor recognition of CD1a presenting self lipid ligands

作者：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; Rossjohn Jamie

来源：Nature Immunology, 2015, 16(3): 258-U215.

DOI：10.1038/ni.3098

A central paradigm in ab T cell-mediated immunity is the simultaneous co-recognition of antigens and antigen-presenting molecules by the ab 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 ab T cells indirectly sense self antigens that are bound to an antigen-presenting molecule.

• 出版日期2015-3