Open AccessCalcium dependency of antigen-specific (T3-Ti) and alternative (T11) pathways of human T-cell activation.
Author(s) -
Michael J. Weiss,
John Daley,
James C. Hodgdon,
Ellis L. Reinherz
Publication year - 1984
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.81.21.6836
Subject(s) - autocrine signalling , biology , microbiology and biotechnology , t cell , interleukin 2 , cytotoxic t cell , monoclonal antibody , antigen , ionomycin , intracellular , cell growth , biochemistry , receptor , antibody , immunology , immune system , in vitro
Human T lymphocytes are activated by two lineage-specific surface components: the antigen/major histocompatibility complex receptor (T3-Ti) and the unrelated T11 molecule. Interaction of either of these with their respective ligands leads to T-cell proliferation via an interleukin 2(IL-2) dependent autocrine mechanism. To begin to characterize the molecular details of the activation process, the role of Ca2+ was examined using human T-cell clones and monoclonal antibodies directed against their surface components. Here, we show that within minutes of triggering either the T3-Ti or T11 molecule, there is a large increase in intracellular Ca2+ concentration, as measured by quin-2 fluorescence. This is essential for induction of T-cell proliferation in inducer, suppressor, and cytotoxic clones and therefore presumably is required at an early step in the autocrine growth pathway. Thus, chelating exogenous Ca2+ with EGTA specifically inhibits proliferation triggered by anti-T3-Ti or anti-T11 monoclonal antibodies, but it does not affect triggering by exogenous IL-2. In addition, the Ca2+ ionophore A23187 can, by itself, initiate clonal proliferation.