DNA VACCINATION PRIMES MHC CLASS I-RESTRICTED, SIMIAN-VIRUS-40 LARGE TUMOR ANTIGEN-SPECIFIC CTL IN H-2(D) MICE THAT REJECT SYNGENEIC TUMORS

We investigated the stimulation of a MHC class I-restricted response o f CTL to the SV40 large tumor Ag (T-Ag) by different vaccination strat egies in H-2(d) and H-2(b) mice, Immunization with plasmid DNA or exog enous T-Ag, or infection with SV40, primed CTL to T-Ag in H-2(b) mice; these three different types of Ag delivery primed T-Ag-specific CTL p opulations with similar epitope/restriction specificities, In H-2(d) m ice, i.m. immunization with plasmid DNA, but neither immunization with exogenous protein Ag nor SV40 infection, primed CTL to T-Ag, T-Ag-spe cific H-2(d) CTL were primed by DNA-based immunization in vivo, expres sed the CD4(-)CD8(+) phenotype, and were L(d)-restricted, In H-2(d) (D BA/2) mice, T-Ag-specific immune responses primed by plasmid DNA injec tion, but not those primed by exogenous T-Ag or SV40 infection, mediat ed CD8(+) CTL-dependent rejection of T-Ag-expressing P815/T tumor graf ts, The data indicate that immunization by plasmid DNA injection is an efficient strategy to induce class I-restricted CTL responses against oncogene-encoded Ags of low immunogenicity that mediate tumor rejecti on.