Smith C A, Williams G T, Kingston R, Jenkinson E J, Owen J J
Department of Anatomy, University of Birmingham Medical School, UK.
Nature. 1989 Jan 12;337(6203):181-4. doi: 10.1038/337181a0.
The receptors found on most T lymphocytes bind to antigen presented on major histocompatibility complex proteins and consist of dimers of alpha- and beta-polypeptides associated with the invariant CD3 complex. 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 TCR alpha- and beta-chain gene segments within the thymus where 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 mechanism. 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.
大多数T淋巴细胞上发现的受体与主要组织相容性复合体蛋白呈递的抗原结合，由与恒定CD3复合体相关的α和β多肽二聚体组成。一个功能完备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（TCR）。这种多样性是由胸腺内TCRα和β链基因片段的重排产生的，受体最初在胸腺中表达。任何携带自身反应性受体的细胞都必须被清除、抑制或失活，以避免破坏性的自身免疫。最近，有力的证据表明，产生这种自身耐受性的一个过程是胸腺内自身反应性细胞通过一种尚未明确的机制进行克隆清除。我们在此表明，用抗CD3抗体使未成熟小鼠胸腺细胞的CD3/TCR复合体结合，会通过内源性凋亡途径导致DNA降解和细胞死亡。因此，TCR与自身抗原结合激活未成熟T细胞中的这一过程，可能是产生克隆清除并进而产生自身耐受性的机制。
