Crystal structures of two H-2Db/glycopeptide complexes suggest a molecular basis for CTL cross-reactivity.
Glithero A., Tormo J., Haurum JS., Arsequell G., Valencia G., Edwards J., Springer S., Townsend A., Pao YL., Wormald M., Dwek RA., Jones EY., Elliott T.
Two synthetic O-GlcNAc-bearing peptides that elicit H-2Db-restricted glycopeptide-specific cytotoxic T cells (CTL) have been shown to display nonreciprocal patterns of cross-reactivity. Here, we present the crystal structures of the H-2Db glycopeptide complexes to 2.85 A resolution or better. In both cases, the glycan is solvent exposed and available for direct recognition by the T cell receptor (TCR). We have modeled the complex formed between the MHC-glycopeptide complexes and their respective TCRs, showing that a single saccharide residue can be accommodated in the standard TCR-MHC geometry. The models also reveal a possible molecular basis for the observed cross-reactivity patterns of the CTL clones, which appear to be influenced by the length of the CDR3 loop and the nature of the immunizing ligand.