PROMISCUOUS AND ALLELE-SPECIFIC ANCHORS IN HLA-DR-BINDING PEPTIDES

The major histocompatibility complex (MHC) class II molecules are high ly polymorphic membrane glycoproteins that bind peptide fragments of p roteins and display them for recognition by CD4+ T cells. To understan d the effect of human MHC class II polymorphism on peptide-MHC interac tion, we have isolated M13 phage from a large M13 peptide display libr ary by selection with DRB10401 and DRB1*1101 molecules, as recently d escribed for DRB10101. Sequence analysis of the peptide-encoding regi on of DR-bound phage led to the identification of position-specific an chor residues, defining motifs for peptide binding to DR molecules. Th e three DR motifs share two anchor residues at relative positions 1 an d 4, while allele-specific anchor residues have been identified at pos ition 6. These results provide a biophysical basis for both the promis cuity and the specificity of peptide recognition by DR molecules.