The crystal structures of K-bm1 and k(bm8) reveal that subtle changes in the peptide environment impact thermostability and alloreactivity

The K-bm1 and K-bm8 natural mutants of the murine MHC class I molecule H-2K (b) were originally identified by allograft rejection. They also bind viral peptides VSV8 and SEV9 with high affinity, but their peptide complexes hav e substantially decreased thermostability, and the K-bm1 complexes do not e licit alloreactive T cell responses. Crystal structures of the four mutant complexes at 1.7-1.9 Angstrom resolution are similar to the corresponding w ild-type K-b structures, except in the vicinity of the mutated residues, wh ich alter the electrostatic potential, topology, hydrogen bonding, and loca l water structure of the peptide binding groove. Thus, these natural K-b mu tations define the minimal perturbations in the peptide environment that al ter antigen presentation to T cells and abolish alloreactivity.