Crystal structure of an MHC class I presented glycopeptide that generates carbohydrate-specific CTL

T cell receptor (TCR) recognition of nonpeptidic and modified peptide antig ens has been recently uncovered but is still poorly understood. Immunizatio n with an H-2K(b)-restricted glycopeptide RGY8-6H-Gal(2) generates a popula tion of cytotoxic T cells that express both alpha/beta TCR, specific for gl ycopeptide, and gamma/delta TCR, specific for the disaccharide, even on gly colipids, The crystal structure of K-b/RGY8-6H-Gal(2) now demonstrates that the peptide and H-2K(b) structures are unaffected by the peptide glycosyla tion, but the central region of the putative TCR binding site is dominated by the extensive exposure of the tethered carbohydrate. These features of t he K-b/RGY8-6H-Gal(2) structure are consistent with the individual ligand b inding preferences identified for the alpha/beta and gamma/delta TCRs and t hus explain the generation of a carbohydrate-specific T cell response.