TCR/CD3 coupling to Fas-based cytotoxicity.
We studied the coupling of the TCR/CD3 complex to a T cell effector function, namely Fas-based T-cell-mediated cytotoxicity. Encounter or re-encounter with antigen was mimicked by treating 5 d mixed lymphocyte culture cells or T cell hybridomas with anti-CD3 antibody. This TCR/CD3 engagement induced swift expression of Fas-based cytotoxicity in these cells. Induction of Fas-based cytotoxicity was Ca(2+)-dependent, while its execution was not; induction was sensitive to macromolecular synthesis inhibitors, in line with a demonstrable increase of the Fas ligand (Fas-L) message. We also used T cell hybridomas transfected with various constructs to dissect the involvement of distinct components of the TCR/CD3 complex. The cytoplasmic domain of the CD3 zeta chain was able to transduce by itself a signal leading to Fas-L expression, unless there were mutations in its activation receptor homology sequence 1 (ARH-1) motifs. On the one hand, these findings are relevant to signal transduction pathways coupled to the TCR/CD3, and on the other hand, to the involvement of Fas-based T cell-mediated cytotoxicity in various physiological and possibly pathophysiological situations.
Vignaux
F
F
Centre d'Immunologie Institut National de la Santé et de la Recherche Médicale-Centre National de la Recherche Scientifique de Marseille-Luminy, France.
Vivier
E
E
Malissen
B
B
Depraetere
V
V
Nagata
S
S
Golstein
P
P
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D017252:CD3 Complex / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019014:fas Receptor
D000954:Antigens, Surface; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor