Majority of peptides binding HLA-A*0201 with high affinity crossreact withother A2-supertype molecules

The A*0201, A*0202, A*0203, A*0206, and A*6802 binding capacity of single a mino acid substitution analogs of known A2-supertype binding peptides and o f large nonredundant peptide libraries was measured. The results were utili zed to rigorously define the peptide binding specificities of these A2-supe rtype molecules. Although each molecule was noted to have unique preference s, large overlaps in specificity were found. The presence of L, I, V, M, A, T, and Q residues in position 2, and L, I, V, M, A, and T residues at the C-terminus of peptide ligands were tolerated by all molecules, Likewise, wh ereas examination of secondary influences on peptide binding revealed allel e specific preferences, shared features could also be identified. These sha red features were utilized to define an A2-supermotif and were noted to cor relate with crossreactivity. Over 70% of the peptides that bound A*0201 wit h high affinity were found to bind at least two other A2-supertype molecule s. Because the A2-supertype molecules studied herein cover the variants mos t common in different major ethnicities, these findings have important impl ications for epitope-based approaches to vaccination, immunotherapy, and th e monitoring of immune responses. (C) American Society fur Histocompatibili ty and Immunogenetics, 2001. Published by Elsevier Science Inc.