Role of a Subdominant H-2K(D)-Restricted SV40 Tumor Antigen Cytotoxic T Lymphocyte Epitope in Tumor Rejection

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SV40-transformed mKSA celts (H-2(d)) readily induce progressively growing tumors in adult syngeneic BALB/c mice while expressing the full complement of H-2(d) 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-2(d)-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-2L(d)-restricted. However, following repeated in vitro restimulation with mKSA cells, CTL emerged which recognized a subdominant H- 2K(d)-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-2K(d)-restricted CTL epitope can participate in the rejection of SV40 tumors in BALB/c mice.

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