ANTIBODIES TO CD3/T-CELL RECEPTOR COMPLEX INDUCE DEATH BY APOPTOSIS IN IMMATURE T-CELLS IN THYMIC CULTURES
ANTIBODIES TO CD3/T-CELL RECEPTOR COMPLEX INDUCE DEATH BY APOPTOSIS IN IMMATURE T-CELLS IN THYMIC CULTURES
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DOI：
10.1038/337181a0
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发表时间：
1989-01-12
期刊：
影响因子：
64.8
通讯作者：
OWEN, JJT
中科院分区：
文献类型：
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作者：
SMITH, CA;WILLIAMS, GT;OWEN, JJT
大多数T淋巴细胞上的受体与主要组织相容性复合体蛋白上的抗原结合，由与不变的α复合体1、2相关的β-和CD3-多肽的二聚体组成。一个完全有效的免疫系统需要一系列具有不同特异性的T细胞抗原受体。这种多样性是通过胸腺3，4受体首次表达的TCRα链和β链基因片段的重排而产生的。任何携带自身反应性受体的细胞都必须被消除、抑制或灭活，以避免破坏性的自身免疫。最近，令人信服的证据表明，产生这种自我耐受的一个过程是通过一种尚未明确的机制5-8克隆删除胸腺内的自身反应细胞。在这里，我们证明了将未成熟的小鼠胸腺细胞的CD3/TCR复合体与抗CD3抗体结合在一起，通过内源性的凋亡途径产生DNA降解和细胞死亡。因此，通过TCR与自身抗原的结合激活未成熟T细胞中的这一过程，可能是产生克隆性删除和随后的自我耐受的机制。
The receptors found on most T lymphocytes bind to antigen presented on major histocompatibility complex proteins and consist of dimers ofα- andβ-polypeptides associated with the invariant CD3 complex1,2. A fully competent immune system requires a diverse array of T-cell antigen receptors (TCRs) with different specificities. This diversity is generated by rearrangement of TCRα- andβ-chain gene segments within the thymus3,4where the receptors are first expressed. Any cells carrying self-reactive receptors must be eliminated, suppressed or inactivated so that destructive autoimmunity is avoided. Recently, compelling evidence has shown that one process involved in producing such self-tolerance is clonal deletion of autoreactive cells within the thymus by an as-yet-undefined mechanism5–8. Here we show that engaging the CD3/TCR complex of immature mouse thymocytes with anti-CD3 antibodies produces DNA degradation and cell death through the endogenous pathway of apoptosis. Activation of this process in immature T cells by the binding of the TCR to self-antigens may therefore be the mechanism which produces clonal deletion and consequently self-tolerance.