Role of a subdominant H-2Kd-restricted SV40 tumor antigen cytotoxic T lymphocyte epitope in tumor rejection.
SV40-transformed mKSA cells (H-2d) readily induce progressively growing tumors in adult syngeneic BALB/c mice while expressing the full complement of H-2d MHC class I antigens. BALB/c mice previously immunized with SV40, soluble SV40 T antigen, or irradiated SV40-transformed syngeneic, allogeneic, or xenogeneic cells reject an mKSA tumor challenge even though these mice have been considered low- or nonresponders to T antigen due to difficulty in demonstrating SV40 T antigen-specific CTL. We have investigated the role of H-2d-restricted CTL in the rejection of SV40 tumors in BALB/c mice. Immunization of BALB/c mice with SV40 induced T antigen-specific CTL which were largely. H-2Ld-restricted. However, following repeated in vitro restimulation with mKSA cells, CTL emerged which recognized a subdominant H-2Kd-restricted epitope corresponding to T antigen residues 499-507. Immunization of BALB/c mice with a recombinant vaccinia virus expressing the T499-507 epitope provided partial protection against a challenge of syngeneic mKSA tumor cells and induced the generation of T499-507-specific CTL. These results indicate that a subdominant H-2Kd-restricted CTL epitope can participate in the rejection of SV40 tumors in BALB/c mice.
Newmaster
R S
RS
Department of Microbiology and Immunology H107, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Mylin
L M
LM
Fu
T M
TM
Tevethia
S S
SS
D000595:Amino Acid Sequence; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D018604:Epitope Mapping; D000939:Epitopes / Q000235:genetics; D006084:Graft Rejection / Q000276:immunology; D006183:H-2 Antigens; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D030361:Papillomavirus Infections / Q000276:immunology*; D013539:Simian virus 40 / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics
D000952:Antigens, Polyomavirus Transforming; D000939:Epitopes; D006183:H-2 Antigens; C024755:H-2K(K) antigen