Structural basis of 2C TCR allorecognition of H-2Ld peptide complexes

MHC class I H-2L(d) complexed with peptide QL9 (or p2Ca) is a high-affinity alloantigen for the 2C TCR. We used the crystal structure of H-2L(d) with a mixture of bound peptides at 3.1 Angstrom to construct a model of the allogeneic 2C-L-d/QL9 complex for comparison with the syngeneic 2C-K-b/dEV8 structure. A prominent ridge on the floor of the L-d peptide-binding groove, not present in K-b, creates a C-terminal bulge in L-d peptides that greatly increases interactions with the 2C beta-chain. Furthermore, weak electrostatic complementarity between Asp77 on the alpha(1) helix of K-b and 2C is enhanced in the allogeneic complex by closer proximity of QL9 peptide residue AspP8 to the 2C HV4 loop.