?? T cell antigen receptor recognition of CD1a presenting self lipid ligands.

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

SUBMITTER: Birkinshaw RW 

PROVIDER: S-EPMC7103088 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature