STRUCTURAL PRINCIPLES THAT GOVERN THE PEPTIDE-BINDING MOTIFS OF CLASS-I MHC MOLECULES

The peptides that bind class I MHC molecules are restricted in length and often contain key amino acids, anchor residues, at particular posi tions. The side-chains of peptide anchor residues interact with the po lymorphic complementary pockets in MHC peptide-binding grooves and pro vide the molecular basis for allele-specific recognition of antigenic peptides. We establish correlations between class I MHC specificities for anchor residues and class I MHC sequence markers that occur at the polymorphic positions Lining the structural pockets. By analyzing the pocket structures of nine crystallized class I MHC molecules and the modeled structures of another 39 class I MHC molecules, we show that c lass I pockets can be classified into families that are distinguishabl e by their common physico-chemical properties and peptide side-chain s electivities. The identification of recurrent structural principles am ong class I pockets makes it possible to greatly expand the repertoire of known peptide-binding motifs of class I MHC molecules. The evoluti onary strategies underlying the emergence of pocket families is briefl y discussed. (C) 1998 Academic Press.