CD1d-lipid antigen recognition by the γδ TCR
Research output: Contribution to journal › Article › Research › peer-review
The T cell repertoire comprises alphabeta and gammadelta T cell lineages. Although it is established how alphabeta T cell antigen receptors (TCRs) interact with antigen presented by antigen-presenting molecules, this is unknown for gammadelta TCRs. We describe a population of human Vdelta1(+) gammadelta T cells that exhibit autoreactivity to CD1d and provide a molecular basis for how a gammadelta TCR binds CD1d-alpha-galactosylceramide (alpha-GalCer). The gammadelta TCR docked orthogonally, over the A pocket of CD1d, in which the Vdelta1-chain, and in particular the germ line-encoded CDR1delta loop, dominated interactions with CD1d. The TCR gamma-chain sat peripherally to the interface, with the CDR3gamma loop representing the principal determinant for alpha-GalCer specificity. Accordingly, we provide insight into how a gammadelta TCR binds specifically to a lipid-loaded antigen-presenting molecule.