title: An HLA-B35-restricted epitope modified at an anchor residue results in an antagonist peptide.
abstract: Peptides associated with HLA-B35 commonly have a proline or occasionally a serine residue in the P2 anchor position of the peptide, with a tyrosine at the C terminus. Based on this motif, we identified an octamer epitope from influenza A matrix protein which is presented by HLA-B35. The requirements for MHC binding and T cell receptor contact have been analyzed using analogs of this peptide with substitutions at positions 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 favored amino acid in this position in B35-associated peptides) considerably enhances binding to HLA-B35 in the T2-B35 cell line, but the peptide is not recognized by the majority of CTL clones and can antagonize recognition of the index peptide. This suggests that a conservative substitution at the P2 anchor position results in a conformational change in the peptide-MHC surface exposed to the T cell receptor.
authors.affiliation: Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, GB.
authors.forename: T
authors.initials: T
authors.lastname: Dong
authors.forename: D
authors.initials: D
authors.lastname: Boyd
authors.forename: W
authors.initials: W
authors.lastname: Rosenberg
authors.forename: N
authors.initials: N
authors.lastname: Alp
authors.forename: M
authors.initials: M
authors.lastname: Takiguchi
authors.forename: A
authors.initials: A
authors.lastname: McMichael
authors.forename: S
authors.initials: S
authors.lastname: Rowland-Jones
mesh_terms: D000595:Amino Acid Sequence; D001667:Binding, Competitive / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D015797:HLA-B35 Antigen / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D009980:Influenza A virus / Q000737:chemistry / Q000276:immunology; D018655:Lymphocyte Count; D007959:Lymphocyte Culture Test, Mixed; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D013234:Stem Cells / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D015797:HLA-B35 Antigen; D010455:Peptides