CHANGES IN MEMBRANE-POTENTIAL OF TARGET-CELLS PROMOTES CYTOTOXIC ACTIVITY OF EFFECTOR T-LYMPHOCYTES

The effector function of CD8(+) lymphocytes depends on recognition by the TcR-CD3 complex of an oligopeptide presented by an MHC class I mol ecule on target cells. Recently it has been shown that MHC class I mol ecules change their conformation upon depolarization of human B lympho blastoid JY cells. We studied here the effects of changes in membrane potential of target cells on the function of cytotoxic T lymphocytes ( CTL). Selective alterations of plasma membrane potential of JY target cells were achieved by treatments with specific ionophore molecules as well as with Na+-K+-ATPase inhibitor, while the cytotoxic lymphocytes were not influenced. The plasma membrane was depolarized by gramicidi n D and ouabain, while hyperpolarization was induced by valinomycin tr eatment. Alterations of the resting membrane potential of target cells in both direction resulted in an enhanced cytotoxic activity. The obs erved changes in cytolytic activities of cytotoxic T effecters may hav e a more general biological significance, namely apoptotic cells becom e depolarized after a given time, moreover neoplastic and virus infect ed cells also frequently show decreased membrane potential. A more eff icient recognition of these cells by CTL is supposed to enhance the ef ficiency of their elimination, as well.