Doyle C, Strominger J L
Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138.
Nature. 1987;330(6145):256-9. doi: 10.1038/330256a0.
The CD4 glycoprotein is expressed on T-helper and cytotoxic lymphocytes which are restricted to class II major histocompatibility complex (MHC) antigens on target cells. Antibody inhibition studies imply that CD4 acts to increase the avidity of effector-target cell interactions. These observations have led to the speculation that CD4 binds to a monomorphic class II antigen determinant, thereby augmenting low affinity T-cell receptor-antigen interactions. However, no direct evidence has been presented indicating that CD4 and class II molecules interact. To address this issue, we have used a vector derived from simian virus 40 (SV40) to express a complementary DNA (cDNA) encoding the human CD4 glycoprotein. When CV1 cells expressing large amounts of the CD4 protein at the cell surface are incubated with human B cells bearing MHC-encoded class II molecules, they are bound tightly to the infected monolayer, whereas mutant B cells which lack class II molecules fail to bind. Furthermore, the binding reaction is specifically inhibited by anti-class II and anti-CD4 antibodies. Thus, the CD4 protein, even in the absence of T-cell receptor-antigen interactions, can interact directly with class II antigens to function as a cell surface adhesion molecule.
CD4糖蛋白在辅助性T淋巴细胞和细胞毒性淋巴细胞上表达，这些细胞受限于靶细胞上的II类主要组织相容性复合体（MHC）抗原。抗体抑制研究表明，CD4的作用是增加效应细胞与靶细胞相互作用的亲和力。这些观察结果引发了一种推测，即CD4与一种单态性II类抗原决定簇结合，从而增强低亲和力的T细胞受体与抗原的相互作用。然而，尚未有直接证据表明CD4与II类分子相互作用。为了解决这个问题，我们使用了一种源自猴病毒40（SV40）的载体来表达编码人CD4糖蛋白的互补DNA（cDNA）。当将在细胞表面大量表达CD4蛋白的CV1细胞与携带MHC编码的II类分子的人B细胞一起孵育时，它们会紧密结合到感染的单层细胞上，而缺乏II类分子的突变B细胞则无法结合。此外，抗II类抗体和抗CD4抗体可特异性抑制这种结合反应。因此，即使在没有T细胞受体与抗原相互作用的情况下，CD4蛋白也能直接与II类抗原相互作用，充当细胞表面粘附分子。
