Orchansky P L, Teh H S
Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
J Immunol. 1994 Jul 15;153(2):615-22.
The first signaling event that occurs after stimulation of the TCR is an increase in the tyrosine phosphorylation of a number of proteins including the TCR-zeta chain and CD3 subunits. It is known that proliferating T cells respond differently to TCR stimulation when compared with naive T cells. Stimulation of the TCR on proliferating T cells has been shown to result in cell death by apoptosis, a process referred to as activation-induced cell death (AICD). In this study we have determined the pattern of tyrosine phosphorylation of TCR-zeta and the CD3 subunits of naive and proliferating CD4- CD8+ T cells that express a transgenic TCR that is specific for the male Ag presented by Db class I molecules after TCR stimulation. AICD in proliferating T cells was mediated by stimulation with anti-TCR/CD3, but not anti-Thy-1, anti-CD8, or anti-Db mAbs. When compared with naive T cells, tyrosine phosphorylation of TCR-zeta was dramatically decreased in proliferating cells. Furthermore, whereas CD3 delta, CD3 epsilon, and CD3 gamma of naive T cells were phosphorylated in a 1:2:1 ratio after TCR stimulation, these subunits in proliferating T cells were tyrosine phosphorylated in a 1:1:0 ratio after TCR stimulation. Altered phosphorylation of these subunits was not caused by the lack of synthesis or amount of these proteins in proliferating cells. This is the first study implicating altered tyrosine phosphorylation of TCR/CD3 subunits in AICD.
TCR 受到刺激后发生的首个信号事件是多种蛋白质（包括 TCR-ζ 链和 CD3 亚基）的酪氨酸磷酸化增加。已知与初始 T 细胞相比，增殖性 T 细胞对 TCR 刺激的反应不同。已表明，增殖性 T 细胞上的 TCR 受到刺激会导致细胞通过凋亡死亡，这一过程称为活化诱导的细胞死亡（AICD）。在本研究中，我们确定了表达转基因 TCR 的初始和增殖性 CD4-CD8+ T 细胞的 TCR-ζ 和 CD3 亚基在 TCR 刺激后针对由 I 类 Db 分子呈递的雄性抗原的酪氨酸磷酸化模式。增殖性 T 细胞中的 AICD 由抗 TCR/CD3 刺激介导，但抗 Thy-1、抗 CD8 或抗 Db mAb 刺激则不能介导。与初始 T 细胞相比，增殖性细胞中 TCR-ζ 的酪氨酸磷酸化显著降低。此外，初始 T 细胞的 CD3δ、CD3ε 和 CD3γ 在 TCR 刺激后以 1:2:1 的比例磷酸化，而增殖性 T 细胞中的这些亚基在 TCR 刺激后以 1:1:0 的比例发生酪氨酸磷酸化。这些亚基磷酸化的改变并非由增殖性细胞中这些蛋白质的合成缺乏或数量不足所致。这是第一项表明 TCR/CD3 亚基酪氨酸磷酸化改变与 AICD 有关的研究。
