The detection of a spleen focus-forming virus neoantigen by lymphocyte-mediated cytolysis.
The existence of a nonvirion tumor-associated cell surface antigen (TASA) on cells transformed with Friend (FLV) on Rauscher (RLV) leukemia virus has been difficult to demonstrate. Antisera raised against classically defined Friend- Moloney-Rauscher antigenic determinants have been shown to react with virus structural proteins coded for by genetic information contained in the lymphatic leukemia or helper (LLV) virus genome. The recent development of nontrans-formed fibroblast cell lines which contain the replication-defective spleen focus-forming virus (SFFV) genome, free of replicating LLV, has allowed investigation of an SFFV-specific antigen. We have applied the techniques of mixed tumor-lymphocyte culture stimulation followed by lymphocyte-mediated cytolysis assays to search for the cell surface expression of an antigen coded expressly by SFFV genetic information. SFFV nonproducer-immune, in vitro activated spleen cells were capable of effecting the lysis of SFFV-containing BALB/c 3T3 and Fischer rat epithelial, cloned cell lines. Normal BALB/c 3T3 and BALB/c 3T3 cells infected with three types of ecotropic LLV were unaffected. Syngeneic FLV and RLV-induced murine leukemia cells were also killed by SFFV nonproducer-immune lymphocytes. In addition, Kirsten sarcoma virus-transformed, replication-defective and replication-rescued BALB/c 3T3 fibroblasts were not susceptible to SFFV antigen-directed cytolysis. Antibody-dependent complement-mediated cytolysis assays using monospecific goat antisera confirmed that SFFV nonproducers lacked cell surface expression of virion structural proteins. These observations suggest that the antigen detected in LMC experiments was not coded for by genetic information contained in the helper component of FLV, and that it represents a true SFFV-specific cell surface antigen. Based upon the recent molecular evaluation of the SFFV genome as consisting of both xenotropic and ecotropic virus sequences, it appears reasonable that xenotropic genetic information may be responsible for expression of the SFFV- specific antigen. Since the replication-defective SFFV genome is also responsible for the malignant transformation associated with FLV-induced erythroleukemia, one might postulate that gene sequences capable of programming transformation may also code for the TASA detected in these studies.
D000818:Animals; D000951:Antigens, Neoplasm / Q000302:isolation & purification*; D000956:Antigens, Viral / Q000302:isolation & purification*; D002462:Cell Membrane / Q000276:immunology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D005260:Female; D005814:Genes, Viral; D005815:Genetic Code; D006378:Helper Viruses / Q000276:immunology; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000276:immunology; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology* / Q000382:microbiology; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D013154:Spleen / Q000382:microbiology; D014764:Viral Proteins / Q000302:isolation & purification
D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D000939:Epitopes; D014764:Viral Proteins