Kearse K P, Roberts J L, Singer A
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Immunity. 1995 Apr;2(4):391-9. doi: 10.1016/1074-7613(95)90147-7.
The present study has examined the molecular events leading to formation of alpha beta dimers in normal murine thymocytes and mature T cells. We demonstrate that TCR assembly proceeds by initial association of TCR alpha with CD3 delta epsilon proteins and by association of TCR beta with CD3 gamma epsilon proteins to form alpha delta epsilon and beta gamma epsilon trimers; these trimers then associate to form alpha delta epsilon-beta gamma epsilon complexes, within which alpha-beta disulfide bond formation occurs. We also show that TCR-associated protein (TRAP) associates uniquely with CD3 gamma epsilon pairs and that formation of beta gamma epsilon trimers occurs subsequent to TRAP dissociation. Importantly, we document that the assembly step that is quantitatively limiting in CD4+ CD8+ thymocytes is the initial association of TCR alpha with CD3 delta epsilon chains, which appears necessary to protect nascent TCR alpha proteins from accelerated degradation within the ER of immature thymocytes.
本研究检测了正常小鼠胸腺细胞和成熟T细胞中导致αβ二聚体形成的分子事件。我们证明，TCR组装通过TCRα与CD3δε蛋白的初始结合以及TCRβ与CD3γε蛋白的结合来进行，以形成αδε和βγε三聚体；然后这些三聚体结合形成αδε-βγε复合物，在其中发生α-β二硫键的形成。我们还表明，TCR相关蛋白（TRAP）仅与CD3γε对结合，并且βγε三聚体的形成发生在TRAP解离之后。重要的是，我们记录到在CD4+CD8+胸腺细胞中定量限制组装步骤的是TCRα与CD3δε链的初始结合，这似乎是保护新生TCRα蛋白免于在未成熟胸腺细胞的内质网中加速降解所必需的。
