Recognition by cytolytic T and K cells: identification in both systems of a divalent cation-independent, cytochalasin A-sensitive step.
Most studies of recognition events in cell-mediated cytolysis have analyzed the conditions that are required to establish mechanically stable binding between effector cells and target cells. This approach has shown that cytolytic T cells require a temperature above 20 degrees C and free divalent cations to bind specifically to target cells. K cells on the other hand were shown to bind to IgG on target cells in the absence of divalent cations at 4 degrees C. In this paper we show that both K cell- and T cell-mediated cytolysis are inhibited by cytochalasin A, if this drug is added to cultures before the effector and target cells have interacted. However, the drug does not block the calcium-dependent lethal hit stage of cytolysis in either system. We then show that in both T cell- and K cell-mediated cytolysis, the cytochalasin A-inhibitable stage can proceed in the absence of divalent cations. We conclude from these data that: 1) both K cell- and T cell-mediated cytolysis have a divalent cation-independent stage, which is inhibitable by cytochalasin A; 2) firm mechanical binding of T effectors to target cells requires divalent cations. It is uncertain if the latter is necessary for cytolysis of whether K cells also have to go through a divalent cation phase before the lethal hit stage. The implications of these findings are discussed, especially as to the possibility that strong binding may not be necessary for T cell-mediated cytolysis.
D000818:Animals; D001666:Binding Sites, Antibody; D002118:Calcium / Q000378:metabolism; D002413:Cations, Divalent; D003572:Cytochalasins / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D007141:Immunoglobulin Fc Fragments; D007694:Killer Cells, Natural / Q000276:immunology*; D008274:Magnesium / Q000378:metabolism; D051379:Mice; D011817:Rabbits; D012756:Sheep; D013601:T-Lymphocytes / Q000276:immunology*; D013696:Temperature
D002413:Cations, Divalent; D003572:Cytochalasins; D007141:Immunoglobulin Fc Fragments; D008274:Magnesium; D002118:Calcium