A PATTERN SEARCH METHOD FOR PUTATIVE ANCHOR RESIDUES IN T-CELL EPITOPES

The binding affinity between an antigenic peptide and its particular m ajor histocompatibility complex (MHC) molecule seems to be largely det ermined by only a few residues. These residues have been called ''anch ors'' because of their property of fitting into ''pockets'' inside the groove of the MHC molecule. To predict natural antigenic epitopes wit hin a longer sequence, it therefore appears to be important to know th e motif or pattern describing the anchors, i.e. the anchors amino acid residue preference and the distance between anchor residues. A large set of MHC class I-restricted peptides has been described. Peptide seq uences vary in length and lack an obvious common sequence motif. For a list of peptides belonging to one type of MHC class I molecule, we de scribe a method to find the most prominent sequence motif with at leas t two anchor residues. Briefly, antigenic sequences are aligned, and t wo anchor positions are searched for, where all anchor residues share a high similarity. The alignments are scored according to the similari ty of their anchor residues. We show that the motifs predicted for the MHC alleles A2.1, B27, K(b), K(d), D(b) are in substantial agreement with experimental data.We derive binding motifs for the MHC class I al leles HLA-A1, A11, B8, B14, H-2L(d) and for the MHC class II alleles I -A(b) and I-A(s). In some cases, higher scores were obtained by allowi ng a slight variation in the number of residues between anchors. There fore, we support the view that the length of epitopes belonging to a p articular class I MHC is not uniform. This method can be used to predi ct the natural short epitope inside longer antigenic peptides and to p redict the epitopes anchor residues. Anchor motifs can be used to sear ch for antigenic regions in sequences of infectious viruses, bacteria and parasites.