McMichael A J, Gotch F M, Santos-Aguado J, Strominger J L
Institute for Molecular Medicine, John Radcliffe Hospital, Oxford, England.
Proc Natl Acad Sci U S A. 1988 Dec;85(23):9194-8. doi: 10.1073/pnas.85.23.9194.
Cytotoxic T lymphocytes (CTL) specific for influenza A virus were prepared from 15 donors. Those with HLA-A2 recognized autologous or HLA-A2-matched B-lymphoblastoid cells in the presence of synthetic peptide representing residues 55-73 or 56-68 of the virus matrix protein sequence. Influenza A virus-specific CTL from donors without HLA-A2 or with an HLA-A2 variant type failed to respond to this peptide. CTL lines specific for HLA-A2 plus peptide did not lyse peptide-treated target cells from HLA-A2 variant donors. They also failed to lyse peptide-treated cells with point mutations that had been inserted into HLA-A2 at positions 62-63, 66, 152, and 156 and, in some instances, mutations at positions 9 and 70. CTL lysed peptide-treated target cells with mutations in HLA-A2 at positions 43, 74, and 107. The results imply that this defined peptide epitope therefore interacts with HLA-A2 in the binding groove so that the long alpha-helices of HLA-A2 make important contact with the peptide at positions 66, 152, and 156. Different amino acids at position 9, which is in the floor of the peptide binding groove of HLA-A2 and the closely related position 70, modulate the peptide interaction so that some T-cell clones react and some do not.
从15名供体中制备了针对甲型流感病毒的细胞毒性T淋巴细胞（CTL）。那些具有HLA - A2的供体在存在代表病毒基质蛋白序列第55 - 73位或56 - 68位残基的合成肽的情况下，能够识别自体或HLA - A2匹配的B淋巴母细胞。来自无HLA - A2或具有HLA - A2变异型的供体的甲型流感病毒特异性CTL对该肽无反应。针对HLA - A2加肽的CTL系不能裂解来自HLA - A2变异型供体的经肽处理的靶细胞。它们也不能裂解在HLA - A2的62 - 63、66、152和156位插入点突变以及在某些情况下9和70位突变的经肽处理的细胞。CTL能裂解在HLA - A2的43、74和107位有突变的经肽处理的靶细胞。结果表明，这个确定的肽表位因此在结合槽中与HLA - A2相互作用，使得HLA - A2的长α螺旋在66、152和156位与肽形成重要接触。在HLA - A2肽结合槽底部的9位以及与之密切相关的70位的不同氨基酸调节肽的相互作用，使得一些T细胞克隆有反应而一些则无反应。
