Signal transducing mechanisms involved in human T cell activation via surface T44 molecules. Comparison with signals transduced via the T cell receptor complex.
Antibodies against the T44 surface molecule have been shown to activate human T cells to produce interleukin 2. The role of Ca2+ in the triggering of the interleukin 2-producing Jurkat T cell line by anti-T44 monoclonal antibody has been investigated. We show that activation is initiated by an increase in the concentration of free cytoplasmic calcium ions [Ca2+]i. Subsequently, we have investigated the mechanism by which perturbation of T44 molecules induces increases of [Ca2+]i in Jurkat cells. We show that the anti-T44-mediated increase in [Ca2+]i can occur only in presence of extracellular Ca2+, since no increment is detectable when extracellular Ca2+ is depleted by EGTA. Thus, it appears that perturbation of T44 molecules, unlike that of T3-Ti antigen receptor complex, fails to mobilize Ca2+ from intracellular stores. As inositol triphosphate is considered the putative mobilizer of Ca2+ from internal stores, we measured the levels of inositol triphosphate and of the other inositol phosphate compounds in Jurkat cells after stimulation with anti-T44 antibodies. In contrast to the stimulation via the T3-Ti antigen receptor complex, stimulation via T44 molecule does not induce increments of all three inositol phosphates. Taken together, these data indicate that stimulation mediated by the T44 molecule proceeds via a mechanism independent from the typical inositol lipid metabolism which does not involve mobilization of Ca2+ from internal stores.
D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007295:Inositol Phosphates; D011948:Receptors, Antigen, T-Cell; D002118:Calcium