Towards the MHC-peptide combinatorics

The exponentially increased sequence information on major histocompatibilit y complex (MHC) alleles points to the existence of a high degree of polymor phism within them. To understand the Functional consequences of MHC alleles , 36 nonredundant MHC-peptide complexes in the protein data bank (PDB) were examined. Induced fit molecular recognition patterns such as those in MHC- peptide complexes are governed by numerous rules. The 36 complexes were clu stered into 19 subgroups based on allele specificity and peptide length. Th e subgroups were further analyzed for identifying common features in MHC-pe ptide binding pattern. The four major observations made during the investig ation were: (1) the positional preference of peptide residues defined by pe rcentage burial upon complex formation is shown for all the 19 subgroups an d thr burial profiles within entries in a given subgroup are found to be si milar; (2) in class I specific 8- and 9-mer peptides, the fourth residue is consistently solvent exposed, however this observation is not consistent i n class I specific 10-mer peptides; (3) an anchor-shift in positional prefe rence is observed towards the C terminal as the peptide length increases in class II specific peptides; and (4) peptide backbone atoms are proportiona tely dominant at the MHC-pepcide interface. (C) American Society for Histoc ompatibility and Immunogenetics, 2001. Published by Elsevier Science Inc.