E1A ONCOGENE EXPRESSION IN TARGET-CELLS INDUCES CYTOLYTIC SUSCEPTIBILITY AT A POST-RECOGNITION STAGE IN THE INTERACTION WITH KILLER LYMPHOCYTES

E1A oncogene expression increases the susceptibility of cells from sev eral species to lysis by natural killer lymphocytes (NK cells), We ask ed whether this E1A-induced cellular phenotypic conversion is specific for NK cell recognition interactions with target cells or whether it results from an E1A effect that is mediated independently of recogniti on, E1A-positive and E1A-negative cell pairs were compared for cytolyt ic susceptibility to other types of killer cells that use recognition mechanisms different from those of NK cells, E1A-positive, NK-suscepti ble target cells were also preferentially lysed by cytotoxic T lymphoc ytes (CTL) that recognize only foreign MHC molecules, lymphokine-activ ated T cells that lack recognition specificity, and CTL whose conventi onal recognition mechanisms were bypassed by lectin treatment of targe t cells, E1A expression increased cellular susceptibility to both majo r mechanisms of killer cell lysis-perforin/granzyme lysis and Fas-depe ndent lysis, Furthermore, anti-Fas antibody lysed E1A-positive, but no t E1A-negative, cells expressing comparable levels of cell surface Fas antigen, These results indicate that a major mechanism by which E1A i nduces cellular susceptibility to lysis involves a stage in the intera ction of killer cells with their targets that follows and is independe nt of cell surface recognition.