Crystal Structure of Vδ1T Cell Receptor in Complex with CD1d-Sulfatide Shows MHC-like Recognition of a Self-Lipid by Human γδ T Cells

The nature of the antigens recognized by γδ Tcells and their potential recognition of major histocompatibility complex (MHC)-like molecules has remained unclear. Members of the CD1 family of lipid-presenting molecules are suggested ligands for Vδ1 TCR-expressing γδ Tcells, the major γδ lymphocyte population in epithelial tissues. We crystallized a Vδ1 TCR in complex with CD1d and the self-lipid sulfatide, revealing the unusual recognition of CD1d by germline Vδ1 residues spanning all complementarity-determining region (CDR) loops, as well as sulfatide recognition separately encoded by nongermline CDR3δ residues. Binding and functional analysis showed that CD1d presenting self-lipids, including sulfatide, was widely recognized by gut Vδ1+ γδ Tcells. These findings provide structural demonstration of MHC-like recognition of a self-lipid by γδ Tcells and reveal the prevalence of lipid recognition by innate-like T cell populations.