title: Majority of peptides binding HLA-A*0201 with high affinity crossreact with other A2-supertype molecules.
abstract: The A*0201, A *0202, A*0203, A*0206, and A*6802 binding capacity of single amino acid substitution analogs of known A2-supertype binding peptides and of large nonredundant peptide libraries was measured. The results were utilized to rigorously define the peptide binding specificities of these A2-supertype molecules. Although each molecule was noted to have unique preferences, 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, whereas examination of secondary influences on peptide binding revealed allele specific preferences, shared features could also be identified. These shared features were utilized to define an A2-supermotif and were noted to correlate with crossreactivity. Over 70% of the peptides that bound A *0201 with high affinity were found to bind at least two other A2-supertype molecules. Because the A2-supertype molecules studied herein cover the variants most common in different major ethnicities, these findings have important implications for epitope-based approaches to vaccination, immunotherapy, and the monitoring of immune responses.
authors.affiliation: Epimmune, Inc., San Diego, CA 92121, USA.
authors.forename: J
authors.initials: J
authors.lastname: Sidney
authors.forename: S
authors.initials: S
authors.lastname: Southwood
authors.forename: D L
authors.initials: DL
authors.lastname: Mann
authors.forename: M A
authors.initials: MA
authors.lastname: Fernandez-Vina
authors.forename: M J
authors.initials: MJ
authors.lastname: Newman
authors.forename: A
authors.initials: A
authors.lastname: Sette
mesh_terms: D000483:Alleles; D020816:Amino Acid Motifs; D001665:Binding Sites; D003429:Cross Reactions; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*
chemical_list: D015789:HLA-A2 Antigen; D010455:Peptides