The specificity of H-2-restricted cytotoxic T lymphocytes directed to AKR/Gross leukemia virus-induced tumors. III. Coordinate alterations in viral gp70 antigen expression and restoration of CTL-susceptibility to insusceptible variant tumors.
Two variant subclones, called cl.18-5 and cl.18-12, were derived from the AKR.H-2bSL1 tumor cell line that were, in contrast to the parental cells, selectively insusceptible to H-2-restricted anti-AKR/Gross virus cytotoxic T lymphocytes (CTL). Cell surface expression of viral envelope (env) and group-specific antigens (gag) on these CTL-resistant variants were analyzed and compared with the expression of these antigens on AKR.H-2bSL1 and two other CTL-susceptible clones, cl.1 and cl.5, also derived from AKR.H-2bSL1. Although normal levels of gag-encoded and H-2 antigens were displayed on the CTL-resistant variants, the expression of five distinct determinants of viral gp70 antigen as defined by monoclonal antibodies was significantly decreased on these CTL-resistant variants relative to their expression on the CTL-susceptible cell lines. However, similar dramatic changes in cell surface gp70 antigen expression were undetectable as defined by anti-gp70-specific antiserum. Immunoprecipitation and gel electrophoretic analysis revealed that gp70 molecules from cl.18-5 cells had a lower m.w. than those of AKR.H-2bSL1, but there were no differences in the m.w. of gp70 antigens from AKR.H-2bSL1, cl.5, and cl.18-12 cells. Expression of the five gp70 antigenic determinants mentioned above was completely restored by exposure of cl.18-5 and cl.18-12 cells to the halogenated pyrimidine, iododeoxyuridine (IudR). Treatment of cl.18-5 and cl.18-12 cells with IudR simultaneously restored CTL susceptibility of these cells to anti-AKR/Gross virus CTL without affecting gag and H-2 antigen expression. Viral gp70 antigen immunoprecipitated from IudR-treated cl.18-5 cells had a mobility slightly lower, but different from that of untreated cl.18-5 cells. Pulse-labeling with [35S]-methionine showed that IudR treatment of cl.18-5 cells caused the expression of an additional high m.w. gp70 precursor protein originally absent in untreated cl.18-5 cells but present on parental AKR.H-2bSL1 cells. Collectively, these results pointed to the involvement of viral gp70 antigenic determinants in the recognition of AKR/Gross virus-induced tumor targets by anti-AKR/Gross virus CTL.
D000406:AKR murine leukemia virus / Q000276:immunology*; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D015683:Gene Products, gag; D006183:H-2 Antigens / Q000276:immunology*; D007065:Idoxuridine / Q000494:pharmacology; D009052:Leukemia Virus, Murine / Q000276:immunology*; D007942:Leukemia, Experimental / Q000276:immunology*; D008297:Male; D051379:Mice; D012191:Retroviridae Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D000954:Antigens, Surface; D000956:Antigens, Viral; D015683:Gene Products, gag; D006183:H-2 Antigens; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins; D007065:Idoxuridine