Antigen-receptor interaction requirement for conjugate formation and lethal-hit triggering by cytotoxic T lymphocytes can be bypassed by protein kinase C activators and Ca2+ ionophores.
We show that phorbol esters and Ca2+ ionophores can trigger the lysis of nonantigen-bearing target cells by cytotoxic T lymphocytes. This effect obviates the requirement for antigen-receptor-mediated recognition of the antigen; the intensity of lysis is dose and Ca2+ dependent and requires contact between cytotoxic T lymphocytes and target cells. Using a fluorescence-activated cell sorter to enumerate cytotoxic T lymphocyte-target cell conjugates, we show that phorbol esters at concentrations that triggered lysis of non-antigen-bearing target cells also increased the number of stable conjugates with these target cells. The results point to the importance of the antigen-nonspecific engagements of cytotoxic T lymphocytes in immunologic surveillance. The data also show that the linkage between the T-cell receptor and antigen is not mandatory for conjugate formation, for the strengthening of conjugates, and for lysis.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004789:Enzyme Activation; D004987:Ethers / Q000494:pharmacology; D015759:Ionomycin; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011493:Protein Kinase C / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004987:Ethers; D011948:Receptors, Antigen, T-Cell; D000001:Calcimycin; D004533:Egtazic Acid; D015759:Ionomycin; D004492:Edetic Acid; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium