title: 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 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.
authors.affiliation: Department of Anatomy, University of Birmingham Medical School, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Smith
authors.forename: G T
authors.initials: GT
authors.lastname: Williams
authors.forename: R
authors.initials: R
authors.lastname: Kingston
authors.forename: E J
authors.initials: EJ
authors.lastname: Jenkinson
authors.forename: J J
authors.initials: JJ
authors.lastname: Owen
mesh_terms: D000818:Animals; D000906:Antibodies; D000936:Antigen-Antibody Complex; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D002470:Cell Survival; D002478:Cells, Cultured; D051379:Mice; D009924:Organ Culture Techniques; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D000906:Antibodies; D000936:Antigen-Antibody Complex; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell