Clayton L K, Lerner A, Diener A C, Hussey R E, Koyasu S, Reinherz E L
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115.
Int J Cancer Suppl. 1992;7:1-5.
Early work on T-cell hybridomas lacking the T-cell-receptor (TCR) sub-unit CD3 eta had suggested a correlation between the presence of CD3 zeta-eta heterodimers and signalling leading to phosphatidyl-inositol (PI) turnover as well as activation-induced cell death. The cloning of CD3 eta has now allowed thorough and direct analysis of the signal transduction properties of CD3 zeta-zeta-, CD3 zeta-eta- and CD3 eta-eta-containing TCRs. We have found that all forms of the TCR are capable of transducing signals leading to PI turnover, Ca2+ mobilization, IL-2 production and cell-cycle arrest. CD3 zeta and CD3 eta utilize the same promoter which yields coordinate expression of both products, so that restricted CD3 eta expression in a sub-population of thymocytes is unlikely. Immunohistochemical methods employing an anti-CD3 eta-specific monoclonal antibody (MAb) show no detectable staining of thymic sections from adult mice, implying at best a low level of constitutive CD3 eta expression. In contrast, CD3 eta expression is readily detected in the majority of cortical thymocytes of CD3 eta transgenic mice using a Thy-1 promoter construct. However, over-expression of CD3 eta in mice transgenic for this polypeptide does not result in increased negative selection in vivo, consistent with the in vitro findings that induction of cell death is not strictly dependent on CD3 eta. Despite earlier reports of the detection of human CD3 eta protein, we find no CD3 eta message in human thymus or T cells. Cloning of the human CD zeta-eta genomic locus has demonstrated approximately 70% homology between the mouse and human genomic sequence, corresponding to the mouse CD3 eta-specific exon. However, translation of the DNA sequence does not result in a homologous amino acid sequence. Thus, there does not appear to be a CD3 eta protein in humans.
早期对缺乏T细胞受体（TCR）亚基CD3η的T细胞杂交瘤的研究表明，CD3ζ-η异二聚体的存在与导致磷脂酰肌醇（PI）周转以及激活诱导的细胞死亡的信号传导之间存在相关性。现在，CD3η的克隆使得对含CD3ζ-ζ、CD3ζ-η和CD3η-η的TCR的信号转导特性进行全面而直接的分析成为可能。我们发现，所有形式的TCR都能够转导导致PI周转、Ca2+动员、白细胞介素-2产生和细胞周期停滞的信号。CD3ζ和CD3η利用相同的启动子，该启动子产生两种产物的协调表达，因此胸腺细胞亚群中CD3η表达受限的可能性不大。使用抗CD3η特异性单克隆抗体（MAb）的免疫组织化学方法显示，成年小鼠胸腺切片未检测到染色，这意味着组成型CD3η表达充其量处于低水平。相比之下，使用Thy-1启动子构建体，在CD3η转基因小鼠的大多数皮质胸腺细胞中很容易检测到CD3η表达。然而，在该多肽转基因小鼠中CD3η的过表达在体内并未导致阴性选择增加，这与体外研究结果一致，即细胞死亡的诱导并不严格依赖于CD3η。尽管早期有关于检测人CD3η蛋白的报道，但我们在人胸腺或T细胞中未发现CD3η信息。人CDζ-η基因组位点的克隆表明，小鼠和人基因组序列之间具有约70%的同源性，对应于小鼠CD3η特异性外显子。然而，DNA序列的翻译并未产生同源氨基酸序列。因此，人类中似乎不存在CD3η蛋白。
