Title : αβ T cell antigen
receptor recognition of
CD1a presenting self lipid ligands
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 othe r lipid ligands were nonpermissive to TCR binding
- The structures of two TCR- CD1a-lipid complexes showed that the TCR docked ove r the A' roof of CD1a in a manne r that precluded direct contact with permissive ligands
- Nonpermissive ligands indirectly inhibited TCR binding by disrupting the TCR- CD1a contact zone
- The exclusive r ecognition 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