Salter R D, Norment A M, Chen B P, Clayberger C, Krensky A M, Littman D R, Parham P
Department of Cell Biology, Stanford University, California 94305.
Nature. 1989 Mar 23;338(6213):345-7. doi: 10.1038/338345a0.
Cytotoxic T lymphocytes (CTL) expressing the CD8 glycoprotein recognize peptide antigens presented by class I major histocompatibility complex (MHC) molecules. This correlation and the absence of CD8 polymorphism led to the hypothesis that CD8 binds to a conserved site of class I MHC molecules. Using a cell-cell binding assay we previously demonstrated specific interaction between human class I MHC (HLA-A,B,C) molecules and CD8. Subsequent analysis of the products of 17 HLA-A,B alleles revealed a natural polymorphism for CD8 binding in the human population. Two molecules, HLA-Aw68.1 and HLA-Aw68.2, which do not bind CD8, have a valine residue at position 245 whereas all other HLA-A,B,C molecules have alanine. Site-directed mutagenesis shows that this single substitution in the alpha 3 domain is responsible for the CD8 binding phenotype and also affects recognition by alloreactive and influenza-specific CTL. Our results indicate that CD8 binds to the alpha 3 domain of class I MHC molecules.
表达CD8糖蛋白的细胞毒性T淋巴细胞（CTL）识别由I类主要组织相容性复合体（MHC）分子呈递的肽抗原。这种相关性以及CD8缺乏多态性导致了这样一种假说，即CD8与I类MHC分子的一个保守位点结合。我们先前使用细胞 - 细胞结合试验证明了人类I类MHC（HLA - A、B、C）分子与CD8之间的特异性相互作用。随后对17个HLA - A、B等位基因产物的分析揭示了人类群体中CD8结合的天然多态性。两种不与CD8结合的分子HLA - Aw68.1和HLA - Aw68.2在第245位有一个缬氨酸残基，而所有其他HLA - A、B、C分子有丙氨酸。定点诱变表明，α3结构域中的这一单取代决定了CD8结合表型，并且还影响同种异体反应性和流感特异性CTL的识别。我们的结果表明，CD8与I类MHC分子的α3结构域结合。
