PEPTIDE BINDING TO MHC CLASS-I MOLECULES - IMPLICATIONS FOR ANTIGENICPEPTIDE PREDICTION

The human mayor histocompatibility complex class I molecule HLA-A2 pre ferentially binds peptides that contain Leu at P2 and Val or Leu at th e C terminus. The other amino acids in the peptide also contribute to binding positively or negatively. It is possible to estimate the bindi ng stability of HLA-A2 complexes containing particular peptides by app lying coefficients, deduced from a large amount of binding data, that quantify the relative contribution of each amino acid at each position . In this review, we describe the molecular basis for these coefficien ts and demonstrate that estimates of binding stability based on the co efficients are generally concordant with experimental measurements of binding affinities. Peptides that contained cysteine were predicted le ss well, possibly because of complications resulting from peptide dime rization and oxidation. Apparently, peptide binding affinity is largel y controlled by the rate of dissociation of the HLA/peptide/beta(2)-mi croglobulin complex, whereas the rate of formation of the complex has less impact on peptide affinity. Although peptides that bind tightly t o HLA-A2, including many antigenic peptides bind much more weakly. The refore, a full understanding of why certain peptides are immunodominan t will require further research.