Crystal structures of two H-2D(b)/glycopeptide complexes suggest a molecular basis for CTL cross-reactivity

Two synthetic O-GlcNAc-bearing peptides that elicit H-2D(b)-restricted glyc opeptide-specific cytotoxic T cells (CTL) have been shown to display nonrec iprocal patterns of cross-reactivity. Here, we present the crystal structur es of the H-2D(b) glycopeptide complexes to 2.85 Angstrom resolution or bet ter. In both cases, the glycan is solvent exposed and available for direct recognition by the T cell receptor (TCR). We have modeled the complex forme d between the MHC-glycopeptide complexes and their respective TCRs, showing that a single saccharide residue can be accommodated in the standard TCR-M HC geometry. The models also reveal a possible molecular basis for the obse rved crossreactivity patterns of the CTL clones, which appear to be influen ced by the length of the CDR3 loop and the nature of the immunizing ligand.