Open AccessAntigen-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.
Author(s) -
Gabriel Berrebi,
Hajime Takayama,
Michail V. Sitkovsky
Publication year - 1987
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.84.5.1364
Subject(s) - cytotoxic t cell , antigen , lysis , microbiology and biotechnology , cytotoxicity , biology , t lymphocyte , cytolysis , conjugate , chemistry , biochemistry , immunology , in vitro , mathematical analysis , mathematics
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.