Alarcón B, Ley S C, Sánchez-Madrid F, Blumberg R S, Ju S T, Fresno M, Terhorst C
Laboratory of Molecular Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
EMBO J. 1991 Apr;10(4):903-12. doi: 10.1002/j.1460-2075.1991.tb08023.x.
The T cell receptor for antigen (TCR) consists of two glycoproteins containing variable regions (TCR-alpha/beta or TCR-gamma/delta) which are expressed on the cell surface in association with at least four invariant proteins (CD3-gamma, -delta, -epsilon and -zeta). CD3-gamma and CD3-delta chains are highly homologous, especially in the cytoplasmic domain. The similarity observed in their genomic organization and their proximity in the chromosome indicate that both genes arose from duplication of a single gene. Here, we provide several lines of evidence which indicate that in human and murine T cells which expressed both the CD3-gamma and CD3-delta chains on their surface, the TCR/CD3 complex consisted of a mixture of alpha beta gamma epsilon zeta and alpha beta delta epsilon zeta complexes rather than a single alpha beta gamma delta epsilon zeta complex. First, a CD3-gamma specific antibody failed to co-immunoprecipitate CD3-delta and conversely, several CD3-delta specific antibodies did not coprecipitate CD3-gamma. Secondly, analysis of a panel of human and murine T cell lines demonstrated that CD3-gamma and CD3-delta were expressed at highly variable ratios on their surface. This suggested that these chains were not expressed as a single complex. Thirdly, CD3-gamma and CD3-delta competed for binding to CD3-epsilon in transfected COS cells, suggesting that CD3-gamma and CD3-delta formed mutually exclusive complexes. The existence of these two forms of TCR/CD3 complexes could have important implications in the understanding of T cell receptor function and its role in T cell development.
抗原T细胞受体（TCR）由两个含有可变区的糖蛋白组成（TCR-α/β或TCR-γ/δ），它们与至少四种恒定蛋白（CD3-γ、-δ、-ε和-ζ）一起表达于细胞表面。CD3-γ和CD3-δ链高度同源，尤其是在胞质结构域。在它们的基因组组织中观察到的相似性以及它们在染色体上的邻近性表明这两个基因都起源于单个基因的复制。在这里，我们提供了几条证据表明，在人源和鼠源T细胞表面同时表达CD3-γ和CD3-δ链时，TCR/CD3复合物由αβγεζ和αβδεζ复合物的混合物组成，而不是单一的αβγδεζ复合物。首先，一种CD3-γ特异性抗体未能共免疫沉淀CD3-δ，反之，几种CD3-δ特异性抗体也不能共沉淀CD3-γ。其次，对一组人源和鼠源T细胞系的分析表明，CD3-γ和CD3-δ在其表面以高度可变的比例表达。这表明这些链不是作为单一复合物表达的。第三，在转染的COS细胞中，CD3-γ和CD3-δ竞争与CD3-ε的结合，表明CD3-γ和CD3-δ形成相互排斥的复合物。这两种形式的TCR/CD3复合物的存在可能对理解T细胞受体功能及其在T细胞发育中的作用具有重要意义。
