Wegener A M, Hou X, Dietrich J, Geisler C
Institute of Medical Microbiology and Immunology, University of Copenhagen, Panum Institute, Denmark.
J Biol Chem. 1995 Mar 3;270(9):4675-80. doi: 10.1074/jbc.270.9.4675.
The T cell antigen receptor (TcR) is a multisubunit complex that consists of at least six different polypeptides. We have recently demonstrated that the CD3-delta subunit cannot substitute for the CD3-gamma subunit in TcR cell surface expression, in spite of significant amino acid homology between these two subunits. To identify CD3-gamma-specific domains that are required for assembly of the complete TcR and for surface expression and function of the TcR, chimeric CD3-gamma/CD3-delta molecules were constructed and expressed in T cells devoid of endogenous CD3-gamma. Substitution of the extracellular domain of CD3-gamma with that of CD3-delta did not allow cell surface expression of the TcR. In contrast, substitution of the transmembrane and/or the intracellular domains of CD3-gamma with those of CD3-delta did allow TcR cell surface expression. These results conclusively demonstrate that the extracellular domain of CD3-gamma plays a unique role in TcR assembly. Functional analyses of the transfectants demonstrated that the intracellular domain of CD3-gamma is required for protein kinase C-mediated down-regulation of TcR but is dispensable for the pattern of tyrosine phosphorylation observed following activation through TcR.
T细胞抗原受体（TcR）是一种多亚基复合体，由至少六种不同的多肽组成。我们最近证明，尽管CD3-δ亚基和CD3-γ亚基之间存在显著的氨基酸同源性，但CD3-δ亚基不能替代CD3-γ亚基参与TcR在细胞表面的表达。为了确定完整TcR组装以及TcR在细胞表面表达和功能所必需的CD3-γ特异性结构域，构建了嵌合的CD3-γ/CD3-δ分子，并在缺乏内源性CD3-γ的T细胞中进行表达。用CD3-δ的胞外结构域替换CD3-γ的胞外结构域后，TcR无法在细胞表面表达。相反，用CD3-δ的跨膜结构域和/或胞内结构域替换CD3-γ的相应结构域后，TcR能够在细胞表面表达。这些结果确凿地证明，CD3-γ的胞外结构域在TcR组装中发挥着独特作用。对转染细胞的功能分析表明，CD3-γ的胞内结构域是蛋白激酶C介导的TcR下调所必需的，但对于通过TcR激活后观察到的酪氨酸磷酸化模式而言并非必需。
