C57BL/10 mice transgenic for HLA-A2 were immunized with either a full-length DNA-construct of the tumor suppressor p53 or with a minigene encoding the p53-derived immunodominant peptide p53(264)LLGRNSFEV272 (L9V). Vaccination with the full-length p53 construct induced potent cytotoxic activity of splenocytes against L9V-pulsed target cells after in vivo re-stimulation. Vaccination with the L9V-encoding minigene likewise induced specific anti-L9V cytotoxicity in vitro. Subsequent experiments revealed that peptide-pulsed dendritic cells were the most efficient cell types for in vitro re-stimulation. In concordance with this, immunization with L9V-pulsed dendritic cells also induced a potent and specific anti-L9V cytotoxic response in vitro. These data show that HLA-A2/peptide-specific cytotoxic immunity can be generated in vivo against the same immunodominant epitope by immunizing either with full-length DNA or with a DNA minigene encoding the immunodominant peptide epitope.