Cytotoxic T-lymphocyte epitope immunodominance in the control of choroid plexus tumors in simian virus 40 large T antigen transgenic mice

The simian virus 40 (SV40) large tumor antigen (Tag) is a virus-encoded onc oprotein which is the target of a strong cytotoxic T-lymphocyte (CTL) respo nse. Three immunodominant H-2(b)-restricted epitopes, designated epitopes I , II/III, and IV, have been defined. We investigated whether induction of C TLs directed against these Tag epitopes might control Tag-induced tumors in SV11(+) (H-2(b)) mice. SV11(+) mice develop spontaneous tumors of the chor oid plexus due to expression of SV40 Tag as a transgene. We demonstrate tha t SV11(+) mice are functionally tolerant to the immunodominant Tag CTL epit opes. CTLs specific for the H-2K(b)-restricted Tag epitope IV were induced in SV11(+) mice following adoptive transfer with unprimed C57BL/6 spleen ce lls and immunization with recombinant vaccinia viruses expressing either fu ll-length Tag or the H-2K(b)-restricted epitope TV as a minigene. In additi on, irradiation of SV11(+) mice prior to adoptive transfer with unprimed C5 7BL/6 spleen cells led to the priming of epitope IV-specific CTLs by the en dogenous Tag. Induction of epitope IV-specific CTLs in SV11(+) mice by eith er approach correlated with increased life span and control of the choroid plexus tumor progression, indicating that CTLs specific for the immunodomin ant Tag epitope IV control the progressive growth of spontaneous tumors ind uced by this DNA virus oncogene in transgenic mice.