Human p53(264-272) HLA-A2 binding peptide is an immunodominant epitope in DNA-immunized HLA-A2 transgenic mice

C57BL/10 mice transgenic for HLA-A2 were immunized with either a full-lengt h DNA-construct of the tumor suppressor p53 or with a minigene encoding the p53-derived immunodominant peptide p53(264)LLGRNSEEV(272) (L9V). Vaccinati on with the full-length p53 construct induced potent cytotoxic activity of splenocytes against L9V-puIsed target cells after in vivo restimulation. Va ccination 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-stimula tion. In concordance with this, immunization with L9V-pulsed dendritic cell s also induced a potent and specific anti-L9V cytotoxic response in vitro. These data show that HLA-A2/peptide-specific cytotoxic immunity can be gene rated in vivo against the same immunodominant epitope by immunizing either with full-length DNA or with a DNA minigene encoding the immunodominant pep tide epitope. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.