title: Recognition of influenza A matrix protein by HLA-A2-restricted cytotoxic T lymphocytes. Use of analogues to orientate the matrix peptide in the HLA-A2 binding site.
abstract: CTL specific for the influenza A virus matrix peptide 57-68 and restricted by HLA-A2 were studied. Their ability to recognize a set of analogue peptides, each of which differed from the natural peptide by a single amino acid, was analyzed. This revealed a core of five amino acids, 61-65, where one or more changes completely abrogated recognition. The glycine at position 61 was the only residue where no substitution was tolerated. Analogue peptides that did not induce CTL-mediated lysis were tested as competitors with the natural peptide; those with substitutions at positions 60, 64, and 65 inhibited, identifying residues that interact with the TCR. Another approach was to test a set of four CTL clones on all of the analogues. Marked differences in recognition by individual CTL clones were observed for several substituted peptides. The data indicate that most of the analogues bind to HLA-A2 with possible differences in fine positioning of the peptide. An alpha helical orientation for the peptide is discussed.
authors.affiliation: Institute for Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: F
authors.initials: F
authors.lastname: Gotch
authors.forename: A
authors.initials: A
authors.lastname: McMichael
authors.forename: J
authors.initials: J
authors.lastname: Rothbard
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D015234:HLA-A Antigens / Q000378:metabolism; D006801:Humans; D009154:Mutation; D010455:Peptides / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000378:metabolism*
chemical_list: D015234:HLA-A Antigens; C031540:M-protein, influenza virus; D010455:Peptides; D014763:Viral Matrix Proteins