Cell-mediated immunity to chemically xenogenized tumors. II. Evidence for accessory function and self-antigen presentation by a highly immunogenic tumor variant.
To determine whether antigen-presenting ability might be involved in the superior immunogenicity of chemically xenogenized tumors over that of parental cells, we tested a murine lymphoma line xenogenized by a triazene derivative for expression of Ia antigens, ability to present soluble antigen in vitro, and production of factor(s) active in a mouse thymocyte assay. Results showed that Ia antigens, absent on nonimmunogenic parental L5178Y cells, were expressed on a xenogenized, highly immunogenic tumor variant (clone D), as detected by immunofluorescence. While the ability of parental cells to stimulate lymphocyte proliferation in vitro was lost on removal of Ia+ cells from the responder population, considerable augmentation of reactivity was observed upon depletion of Ia+ cells from the population of splenocytes responding to the xenogenized cells. Under these conditions, stimulation was blocked by anti-Ia antibodies, or an anti-L3T4 reagent or antibodies to the novel antigenic determinants induced by xenogenization. In addition, no stimulating activity was observed following exposure of clone D cells to glutaraldehyde or lysosomotropic agents such as chloroquine and ammonia. When the ability of clone D cells to present ovalbumin in vitro was assayed, it was found that the xenogenized cells could present the soluble antigen to specifically primed lymphocytes. Moreover, clone D cells could substitute for splenic adherent cells in the proliferative reaction of splenocytes to concanavalin A. Finally, when the supernate from clone D-cell culture pulsed with phorbol myristic acetate was tested in a mouse thymocyte assay, considerable IL-1-like activity was disclosed.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000950:Antigens, Ly / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D005976:Glutaral / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007111:Immunity, Cellular; D007375:Interleukin-1 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008223:Lymphoma / Q000276:immunology; D008247:Lysosomes / Q000187:drug effects; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology*; D012995:Solubility; D014226:Triazenes / Q000494:pharmacology
D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000951:Antigens, Neoplasm; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D014226:Triazenes; D005976:Glutaral