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Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures

Abstract

The receptors found on most T lymphocytes bind to antigen presented on major histocompatibility complex proteins and consist of dimers of α- and β-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 TCR α- and β-chain gene segments within the thymus3,4 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 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.

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Smith, C., Williams, G., Kingston, R. et al. Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures. Nature 337, 181–184 (1989). https://doi.org/10.1038/337181a0

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