Mutants in signal transduction through the T-cell antigen receptor.
Mutants of an untransformed helper T-cell clone have been derived by chemical mutagenesis followed by selection for cells incapable of proliferating in response to antigen or anti-CD3. The selection was designed to enrich cells bearing mutations distal to the T-cell antigen receptor. The mutants express normal levels of functional T-cell receptors but are uncoupled from cellular responses, including gene induction, lymphokine secretion, proliferation, and phosphatidylinositol turnover. Responses to phorbol ester plus calcium ionophore and to interleukin-2 are unimpaired. Responses to antigen were restored by fusion with a T-cell receptor-negative thymoma, making the mutants valuable for investigating the mechanisms that couple T-cell receptor stimulation to the induction of second messengers and subsequent physiologic responses.
Wong
J G
JG
Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Rao
A
A
D000818:Animals; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis / Q000276:immunology; D017252:CD3 Complex; D002460:Cell Line; D002999:Clone Cells; D015870:Gene Expression; D007376:Interleukin-2 / Q000096:biosynthesis; D007377:Interleukin-3 / Q000096:biosynthesis; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D009154:Mutation; D010716:Phosphatidylinositols / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000941:Antigens; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007376:Interleukin-2; D007377:Interleukin-3; D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate