Crosslinking of Surface Antigens Causes Mobilization of Intracellular Ionized Calcium in T Lymphocytes

• Published in: Proceedings of the National Academy of Sciences - PNAS 1987-03, Vol.84 (5), p.1384-1388
• Main Authors: Ledbetter, Jeffrey A., June, Carl H., Grosmaire, Laura S., Rabinovitch, Peter S.
• Format: Article
• Language: English
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Animals; Antibodies; Antibodies, Monoclonal; Antigens; Antigens, Differentiation, B-Lymphocyte; Antigens, Surface - immunology; Biological and medical sciences; Calcium; Calcium - metabolism; Cells, Cultured; Crosslinking; Egtazic Acid - pharmacology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Immunobiology; Mice; Organs and cells involved in the immune response; Physiological regulation; Receptors; Surface antigens; T lymphocytes; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Toxins; Whooping cough
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.5.1384

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+]iincrease 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+]iincrease 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.