Matsui M, Hioe C E, Frelinger J A
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill 27599.
Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):674-8. doi: 10.1073/pnas.90.2.674.
To evaluate the contribution of the major histocompatibility complex class I pockets to the binding of self-peptides recognized by alloreactive cytotoxic T-lymphocyte (CTL) clones, we have constructed an extensive library of HLA-A2 mutants with different amino acid substitutions in each of the six pockets. When these mutants were tested in cytotoxicity assays with a panel of HLA-A2-specific alloreactive CTL clones, each CTL clone showed a unique pattern of reactivity, implying the different contributions of each pocket to binding individual peptides. We noted that the majority of the mutants in pocket B significantly affect recognition by the CTL clones. Unexpectedly, the mutations influencing allorecognition are found in all other pockets as well. Overall, this study demonstrates that each of the six peptide-binding pockets plays an important and distinct role in binding of self-peptides required for recognition of the HLA-A2 molecule by alloreactive CTLs.
为了评估主要组织相容性复合体I类口袋对同种异体反应性细胞毒性T淋巴细胞(CTL)克隆识别的自身肽结合的贡献,我们构建了一个广泛的HLA - A2突变体文库,其中六个口袋中的每一个都有不同的氨基酸替换。当用一组HLA - A2特异性同种异体反应性CTL克隆在细胞毒性试验中测试这些突变体时,每个CTL克隆都表现出独特的反应模式,这意味着每个口袋对结合单个肽的贡献不同。我们注意到,口袋B中的大多数突变体显著影响CTL克隆的识别。出乎意料的是,影响同种异体识别的突变也在所有其他口袋中被发现。总体而言,这项研究表明,六个肽结合口袋中的每一个在同种异体反应性CTL识别HLA - A2分子所需的自身肽结合中都发挥着重要且独特的作用。