IMMUNOLOGICAL CHARACTERIZATION OF TUMOR-REJECTION ANTIGENS ON ULTRAVIOLET-LIGHT-INDUCED TUMORS ORIGINATING IN THE CB6F(1) MOUSE

Six ultraviolet-light(UV)-induced tumors of (BALB/cxC57BL/6)F-1 (H-2(d /b)) mouse origin were analyzed for the effector T cell subsets involv ed in tumor rejection, the MHC class I to which cytolytic T lymphocyte s (CTL) are restricted, and the effect of UV radiation on tumor reject ion, to characterize their tumor-rejection antigens (TRA) recognized b y CTL. All tumors were rejected in syngeneic normal mice but grew prog ressively in nude mice. CD8+ T cells mediated the antitumor responses for all tumors and CD4+ T cells could also do so for one tumor 6.1B. E ach tumor induced potent CTL that recognized the specific TRA in prefe rential association with MHC class I haplotypes not from H-2(b) but fr om H-2(d); that is, K-d, D-d or L(d). Profiles of TRA expression on tw o tumors were obtained by the analyses of their antigen-loss variants. female 1A codominantly expressed at least four distinct TRA associate d with K-d, all of which induced CTL. On the other hand, UV male 1 had at least two distinct TRA, one of which, associated with K-d, exclusi vely induced CTL. However, in the absence of the dominant TRA, another TRA associated with L(d) on R95C, a variant of UV male, 1, induced CT L. Unlike other tumors, R95C grew progressively in short-term-UV-irrad iated syngeneic mice. Nude mice reconstituted with a combination of CD 4+ T cells from short-term-UV-irradiated mice and CD8+ T cells from no rmal mice did not reject R95C. An increase in the former T cell popula tion led the reconstituted mice to reject the tumor. These findings su ggest some functional defects of CD4+ T cells rather than the generati on of suppressor cells in short-term-UV-irradiated mice. The UV-induce d tumors used in the present study provide a unique system for analyzi ng the preferential sorting of TRA as well as for elucidation of the T RA itself.