Role of a Subdominant H-2Kd-Restricted SV40 Tumor Antigen Cytotoxic T Lymphocyte Epitope in Tumor Rejection

Abstract

SV40-transformed mKSA cells (H-2d) readily induce progressively growing tumors in adult syngeneic BALB/c mice while expressing the full complement ofH-2dMHC 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 repeatedin vitrorestimulation 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 T499–507epitope 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.