Vivier E, Morin P, Tian Q S, Daley J, Blue M L, Schlossman S F, Anderson P
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
J Immunol. 1991 Feb 15;146(4):1142-8.
Recent evidence suggests that the zeta-subunit of the TCR complex plays a critical role in transducing signals initiated by the Ag receptor heterodimer. Because thymic maturation involves specific interactions between the TCR complex and thymic stromal cells, the zeta-subunit has been postulated to also play a role in this process. To assess the potential for zeta to contribute to thymocyte maturation, we have used an anti-zeta mAb (TIA-2) to quantitate its expression in mature (CD3bright) and immature (CD3dim and CD3-) populations of human thymocytes. Using both flow cytometric and immunoblotting analysis, we found that the relative expression of TCR-zeta varied directly with the surface expression of CD3. Importantly, TCR-zeta was detected in the majority of CD3- thymocytes, indicating that its expression precedes the surface appearance of CD3:TCR. In thymocytes, TCR-zeta was found to be constitutively phosphorylated on tyrosine residues. The relative expression of phospho-zeta varied directly with the maturational stage of the thymocyte, with the mature (CD3bright), single positive cells accounting for most of the phospho-zeta found in the human thymus. The expression of phospho-zeta could be significantly increased by activating thymocytes with mAb reactive with either CD3 or CD2. These results suggest that TCR-zeta is functionally linked to the major thymocyte activation receptors.
近期证据表明，TCR复合物的ζ亚基在转导由抗原受体异二聚体启动的信号中起关键作用。由于胸腺成熟涉及TCR复合物与胸腺基质细胞之间的特异性相互作用，因此推测ζ亚基在这一过程中也发挥作用。为了评估ζ对胸腺细胞成熟的潜在作用，我们使用了一种抗ζ单克隆抗体（TIA-2）来定量其在人胸腺细胞成熟（CD3bright）和未成熟（CD3dim和CD3-）群体中的表达。通过流式细胞术和免疫印迹分析，我们发现TCR-ζ的相对表达与CD3的表面表达直接相关。重要的是，在大多数CD3-胸腺细胞中检测到了TCR-ζ，这表明其表达先于CD3:TCR的表面出现。在胸腺细胞中，发现TCR-ζ的酪氨酸残基持续磷酸化。磷酸化ζ的相对表达与胸腺细胞的成熟阶段直接相关，成熟的（CD3bright）单阳性细胞占人胸腺中发现的大部分磷酸化ζ。用与CD3或CD2反应的单克隆抗体激活胸腺细胞可显著增加磷酸化ζ的表达。这些结果表明，TCR-ζ在功能上与主要的胸腺细胞激活受体相关联。
