Crosslinking of surface antigens causes mobilization of intracellular ionized calcium in T lymphocytes.
Antibodies binding to a large subset of T-cell differentiation antigens, including CD2, CD4, CD5, CD6, CD7, CD8, Tp44, and CDw18, cause an increase in the cytoplasmic calcium concentration [( Ca2+]i) after the antigens are crosslinked on the cell surface. Similar crosslinking-induced signals were seen for a subset of mouse thymocyte differentiation antigens. The various antigens on human T cells differed in the extent of crosslinking required for generating the calcium signal, as evidenced by comparisons with monoclonal versus polyclonal second-step antibody. The [Ca2+]i increase that occurs after crosslinking represents mobilization of cytoplasmic calcium since the initial component of the signal is resistant to depletion of extracellular calcium by chelation with EGTA. The [Ca2+]i increase is completely inhibited by pretreatment of cells with pertussis toxin, indicating that a substrate for pertussis toxin regulates the signal transduction. Crosslinking of antigens other than the CD3/T-cell receptor complex did not result in T-cell proliferation. Crosslinking of CD2 and Tp44, but not other antigens, resulted in expression of functional interleukin 2 receptors. Comparisons of three different anti-CD3 antibodies showed that a second calcium signal was generated by crosslinking, even when the anti-CD3 antibodies were used at optimal concentrations.
D000818:Animals; D000906:Antibodies; D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D051379:Mice; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D004533:Egtazic Acid; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium