AN HLA-B35-RESTRICTED EPITOPE MODIFIED AT AN ANCHOR RESIDUE RESULTS IN AN ANTAGONIST PEPTIDE

Peptides associated with HLA-B35 commonly have a proline or occasional ly a serine residue in the P2 anchor position of the peptide. with a t yrosine at the C terminus. Based on this motif, we identified an octam er epitope from influenza A matrix protein which is presented by HLA-B 35. The requirements for MHC binding and T cell receptor contact have been analyzed using analogs of this peptide with substitutions at posi tions 1. 2. 4. 7 and 8. The natural epitope contains a serine residue at P2 of the peptide. Substitution of this residue with proline (the f avored amino acid in this position in B35-associated peptides) conside rably enhances binding to HLA-B35 in thc T2-B35 cell line, but the pep tide is not recognized by the majority of CTL clones and can antagoniz e recognition of the index peptide. This suggests that a conservative substitution at the P2 anchor position results in a conformational cha nge in the peptide-MHC surface exposed to the T cell receptor.