Takahama Y, Suzuki H, Katz K S, Grusby M J, Singer A
Syntex Institute of Immunology, Niihari, Japan.
Nature. 1994 Sep 1;371(6492):67-70. doi: 10.1038/371067a0.
The developmental fate of immature thymocytes is determined by the specificity of their T-cell antigen receptors (TCRs). Immature CD4+8+ thymocytes are positively selected to differentiate into mature T cells by recognition of peptides associated with major histocompatibility complex (MHC) encoded molecules on thymic epithelial cells. But neither the identity of molecules transducing positive selection signals nor the nature of the signals themselves is fully known. Here we report that direct ligation of TCR molecules by monoclonal antibodies specific for either clonotypic or CD3 chains can signal immature thymocytes to differentiate into mature CD4+8- T cells, even in the absence of MHC expression and MHC-dependent CD4 co-receptor signalling. Moreover, we show that TCR engagement induces positive selection signals only in the absence of TCR aggregation and that TCR aggregation is inhibitory for positive selection. Thus, low valency of TCR crosslinking is a critical parameter, distinguishing positive selection from other TCR-mediated signalling events.
未成熟胸腺细胞的发育命运由其T细胞抗原受体（TCR）的特异性决定。未成熟的CD4+8+胸腺细胞通过识别与胸腺上皮细胞上主要组织相容性复合体（MHC）编码分子相关的肽段而被阳性选择，进而分化为成熟T细胞。但是，转导阳性选择信号的分子身份以及信号本身的性质都尚未完全明确。在此，我们报告称，用针对克隆型或CD3链的单克隆抗体直接连接TCR分子，即便在没有MHC表达和MHC依赖性CD4共受体信号传导的情况下，也能够促使未成熟胸腺细胞分化为成熟的CD4+8-T细胞。此外，我们还表明，TCR结合仅在不存在TCR聚集的情况下诱导阳性选择信号，而TCR聚集对阳性选择具有抑制作用。因此，TCR交联的低价性是一个关键参数，它将阳性选择与其他TCR介导的信号事件区分开来。
