Transmembrane signalling via the T cell antigen receptor heterodimer and the CD2 antigen. A synergistic pathway for activation of T cells.
T cell surface proteins involved in transmembrane signalling resulting in the activation of T cells were investigated utilizing as probes monoclonal antibodies directed at T cell surface antigens. Here we report that mAbs that react with a framework determinant of alpha/beta heterodimer of T cell receptor for antigen, anti-TCR-1, and those with the SRBC-binding epitope of the CD2 antigen, OKT11, are synergistic in promoting T cell proliferation. The proliferative response is dependent upon crosslinking of anti-TCR-1 and OKT11, and is associated with a significant increase in the concentration of intracellular free calcium in T cells. Moreover, EGTA and a direct (staurosporine) or a competitive (1-[5-isoquinolinylsulfonyl]-2-methyl piperazine) inhibitor of protein kinase C prevents T cell proliferation accomplished with crosslinked anti-TCR-1 and OKT11. Our findings, in addition to demonstrating the synergism between the signals initiated via the T cell receptor for antigen and the CD2 antigen, suggest a role for calcium and protein kinase C in the transduction of signals generated with crosslinked anti-TCR-1 and OKT11.
Suthanthiran
M
M
Rogosin Institute, New York.
D000470:Alkaloids / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018801:CD2 Antigens; D002118:Calcium / Q000378:metabolism; D003432:Cross-Linking Reagents; D004306:Dose-Response Relationship, Immunologic; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D011971:Receptors, Immunologic / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology
D000470:Alkaloids; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D003432:Cross-Linking Reagents; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D004533:Egtazic Acid; D011493:Protein Kinase C; D019311:Staurosporine; D002118:Calcium