A cluster of mutations in HLA-A2 alpha 2 helix abolishes peptide recognition by T cells.

Journal article

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: Moots, R; Matsui, M; Pazmany, L; Mcmichael, A; Frelinger, J

• Publication status: Published
• Journal: Immunogenetics
• Volume: 34
• Issue: 3
• Pages: 141-148
• Publication date: 1991-01-01
• DOI: 10.1007/bf00205816
• EISSN: 1432-1211
• ISSN: 0093-7711
• Language: English
• Keywords: Mutation; Humans; Transfection; HLA-A2 Antigen; Viral Proteins; Influenza A virus; Protein Conformation; Gene Expression; Structure-Activity Relationship; T-Lymphocytes, Cytotoxic; Cell Line