title: A cluster of mutations in HLA-A2 alpha 2 helix abolishes peptide recognition by T cells.
abstract: In order to investigate the regions of HLA-A2 that control peptide-specific cytotoxic T lymphocyte (CTL) recognition, 37 HLA-A2 genes coding for 50 point mutations that span the alpha 2 helix were synthesized by the technique of saturation mutagenesis. Twenty-nine of these genes, which code for 41 point mutations, were transfected into C1R cells and used as targets in cytotoxicity assays, in the presence of influenza-A matrix peptide 58-68 with specific CTL as effectors. All the transfectants were recognized fully by matrix peptide-specific CTL apart from those with amino acid substitutions at positions 152, 154, 155, 156, or 161, which led to a total loss of recognition and those with mutations at residue 27 or a double mutation at 138 and 150, which were recognized in an intermediate manner. The clustering of the crucial residues that emerges may reflect direct interaction of their side-chains with peptide or the CTL receptor.
authors.affiliation: Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Moots
authors.forename: M
authors.initials: M
authors.lastname: Matsui
authors.forename: L
authors.initials: L
authors.lastname: Pazmany
authors.forename: A J
authors.initials: AJ
authors.lastname: McMichael
authors.forename: J A
authors.initials: JA
authors.lastname: Frelinger
mesh_terms: D002460:Cell Line; D015870:Gene Expression; D015789:HLA-A2 Antigen / Q000235:genetics* / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D009154:Mutation; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014764:Viral Proteins / Q000276:immunology
chemical_list: D015789:HLA-A2 Antigen; D014764:Viral Proteins