Immunological characterization of tumor-rejection antigens on ultraviolet-light-induced tumors originating in the CB6F1 mouse.
Six ultraviolet-light(UV)-induced tumors of (BALB/c x C57BL/6)F1 (H-2d/b) mouse origin were analyzed for the effector T cell subsets involved in tumor rejection, the MHC class I to which cytolytic T lymphocytes (CTL) are restricted, and the effect of UV radiation on tumor rejection, to characterize their tumor-rejection antigens (TRA) recognized by CTL. All tumors were rejected in syngeneic normal mice but grew progressively 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. Each tumor induced potent CTL that recognized the specific TRA in preferential association with MHC class I haplotypes not from H-2b but from H-2d; that is, Kd, Dd or Ld. Profiles of TRA expression on two tumors were obtained by the analyses of their antigen-loss variants. Female 1A codominantly expressed at least four distinct TRA associated with Kd, all of which induced CTL. On the other hand, UV male 1 had at least two distinct TRA, one of which, associated with Kd, exclusively induced CTL. However, in the absence of the dominant TRA, another TRA associated with Ld on R95C, a variant of UV male, 1, induced CTL. Unlike other tumors, R95C grew progressively in short-term-UV-irradiated syngeneic mice. Nude mice reconstituted with a combination of CD4+ T cells from short-term-UV-irradiated mice and CD8+ T cells from normal mice did not reject R95C. An increase in the former T cell population led the reconstituted mice to reject the tumor. These findings suggest some functional defects of CD4+ T cells rather than the generation of suppressor cells in short-term-UV-irradiated mice. The UV-induced tumors used in the present study provide a unique system for analyzing the preferential sorting of TRA as well as for elucidation of the TRA itself.
Kitajima
T
T
Department of Dermatology, Faculty of Medicine, Kyoto University, Japan.
Iwashiro
M
M
Kuribayashi
K
K
Imamura
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D005260:Female; D006084:Graft Rejection; D006649:Histocompatibility Antigens / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009381:Neoplasms, Radiation-Induced / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014466:Ultraviolet Rays
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015704:CD4 Antigens; D016827:CD8 Antigens; D006649:Histocompatibility Antigens; C029237:tumor-associated transplantation antigen