Crystal Structure of an MHC Class I Presented Glycopeptide that Generates Carbohydrate-Specific CTL

Abstract

T cell receptor (TCR) recognition of nonpeptidic and modified peptide antigens has been recently uncovered but is still poorly understood. Immunization with an H-2K b-restricted glycopeptide RGY8-6H-Gal 2 generates a population of cytotoxic T cells that express both α/β TCR, specific for glycopeptide, and γ/δ TCR, specific for the disaccharide, even on glycolipids. 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 glycosylation, but the central region of the putative TCR binding site is dominated by the extensive exposure of the tethered carbohydrate. These features of the K b/RGY8-6H-Gal 2 structure are consistent with the individual ligand binding preferences identified for the α/β and γ/δ TCRs and thus explain the generation of a carbohydrate-specific T cell response.