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 several species to lysis by natural killer lymphocytes (NK cells). We asked 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 recognition. E1A-positive and E1A-negative cell pairs were compared for cytolytic susceptibility to other types of killer cells that use recognition mechanisms different from those of NK cells. E1A-positive, NK-susceptible target cells were also preferentially lysed by cytotoxic T lymphocytes (CTL) that recognize only foreign MHC molecules, lymphokine-activated T cells that lack recognition specificity, and CTL whose conventional recognition mechanisms were bypassed by lectin treatment of target cells. E1A expression increased cellular susceptibility to both major mechanisms of killer cell lysis-perforin/granzyme lysis and Fas-dependent lysis. Furthermore, anti-Fas antibody lysed E1A-positive, but not E1A-negative, cells expressing comparable levels of cell surface Fas antigen. These results indicate that a major mechanism by which E1A induces cellular susceptibility to lysis involves a stage in the interaction of killer cells with their targets that follows and is independent of cell surface recognition.
Cook
J L
JL
Robert W Lisle Research Laboratory in Immunology and Tumor Cell Biology, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206, USA.
Potter
T A
TA
Bellgrau
D
D
Routes
B A
BA
D017500:Adenovirus E1A Proteins / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D015870:Gene Expression / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051381:Rats; D011916:Rats, Inbred F344; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019014:fas Receptor / Q000235:genetics
D017500:Adenovirus E1A Proteins; D019014:fas Receptor