The specificity of H-2-restricted cytotoxic T lymphocytes directed to AKR/Gross leukemia virus-induced tumors. II. Altered gp70 display and production of noninfectious virus particles by an insusceptible variant tumor.
Derived from the susceptible AKR.H-2bSL1 tumor cell line, a variant tumor subclone, cl.18-5, was selectively insusceptible to H-2-restricted anti-AKR/Gross virus cytotoxic T lymphocytes (CTL) due to its failure to be recognized. In this study, the expression of virus-related products by variant cl.18-5 cells was compared to that of AKR.H-2bSL1 cells and a susceptible clone, as an approach towards defining the virus-associated antigens recognized by anti-AKR/Gross virus CTL. Despite the type specificity of the CTL, cl.18-5 displayed normal levels of the group-specific antigen (gag) encoded proteins p30, p15, p12 and p10, and the gag-associated Gross cell surface antigen. These results were confirmed by fluorescence-activated cell sorter analysis employing monoclonal antibodies specific for either AKR p12 or the cell surface glycosylated form of AKR ecotropic gag product. In contrast, cl.18-5 was variably less sensitive than AKR.H-2bSL1 to the action of complement and xenogeneic antisera directed against the envelope (env) product gp70. In addition, a panel of five monoclonal antibodies to gp70, which detect distinct endogenous ecotropic viral determinants, lysed AKR.H-2bSL1, but not cl.18-5 cells. However, absorption experiments indicated that cl.18-5 did express near normal levels of these specificities, suggesting an alteration in the orientation or topographical distribution of these determinants. Consistent with an inappropriate display of env products, cl.18-5 was found to be deficient in the production of infectious ecotropic leukemia virus. The particulate fraction of the cell-free supernatant of cl.18-5 contained normal levels of reverse transcriptase activity, indicating that noninfectious viral particles were being produced. Collectively, these results point to an association between recognition by anti-AKR/Gross virus CTL and the expression of ecotropic gp70 required for infectivity of virus.
D000406:AKR murine leukemia virus / Q000254:growth & development / Q000276:immunology; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D000939:Epitopes; D005815:Genetic Code; D014644:Genetic Variation; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology; D007113:Immunity, Innate; D007942:Leukemia, Experimental / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D008907:Mink; D011817:Rabbits; D051381:Rats; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D000956:Antigens, Viral; D000939:Epitopes; D006183:H-2 Antigens; D014759:Viral Envelope Proteins