Antigenic Specificities of the Cellular Immune Response of C57BL/6 Mice to the Moloney Leukemia/Sarcoma Virus Complex

Abstract

The antigenic specificities of the cellular immune response against MoLV-MSV-induced tumors in C57BL/6 mice were studied by using a variety of purified MoLV virion proteins. Cellular reactivity, as assessed by the ability of purified proteins to induce T cell proliferation, was primarily directed against the virion envelope glycoprotein and to a lesser extent against p12. No blastogenesis was detectable with the viral p10, p15, or p30 proteins. The optimal gp71 and p12 antigen concentrations required for 50% of maximal responses were 0.036 and 0.013 nmoles per 5 × 10⁵ cells per 0.2 ml, respectively. Blastogenesis was dependent upon the presence of T cells, but was apparently independent of the presence of macrophages. The antigenic specificity of cellular cytotoxicity was assessed by microcytotoxicity assays by using transformed nonproducer and producer cell lines with a various virus serotypes. The results demonstrated that cytotoxicity was immunologically type-specific for MoLV serotype of virus and is dependent upon the expression of the MoLV viral envelope glycoprotein gp71. The requirement for gp71 cytotoxicity was further assessed by antigen-blocking experiments. These results demonstrate that only MoLV gp71 could significantly block cytotoxicity (τ80%), whereas no blocking was seen with RLV gp71, MoLV p30, p15, p12, or p10, suggesting that the major cytotoxic response is directed against MoLV gp71. The temporal relationships of the cellular as well as the humoral immune responses related to tumor development and regression are also described.