A cluster of mutations in HLA-A2 alpha 2 helix abolishes peptide recognition by T cells.
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.
Moots
R J
RJ
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.
Matsui
M
M
Pazmany
L
L
McMichael
A J
AJ
Frelinger
J A
JA
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
D015789:HLA-A2 Antigen; D014764:Viral Proteins