Overall the S598 determinant displays greater complementarity for the antigen binding cleft of H-2K b in its N-terminal region, with few stabilizing interactions observed between the HC and positions 6 and 7. (Figure S3B, D; Table S2 ). Nevertheless, a pocket is observed between the a-2 helix and the peptide near position 3 in the index structure that is filled by the steric bulk of Tyr-3 in the Q600Y structure ( Figure 5C,F) . This increase in surface complementarity and the greater number of observed interactions resulting from the Q3RY3 mutation would account for the enhanced thermostability (,10uC) measured for the H-2K b /S598 Q600Y -Aba complex by circular dichroism (Figure 1 ). This increase in complementarity of the MHC for S598 Q600Y and the greater stability of the resulting complex were predicted from comparisons of the WT determinant complex with existing structures of H-2K b bound with peptides similar to S598 and possessing the consensus tyrosine anchor residue at position 3, as well as another aromatic residue at position 5.