Immunization of Lewis Rats with A Prostate Cancer Xenoantigen Elicits Predominantly Xenoantigen Epitope-Specific T Cell Responses

1174 Prostatic acid phosphatase (PAP) is a prostate cancer tumor antigen and a prostate-specific protein shared by rats and humans. Previous studies have demonstrated that rats immunized with the human homologue (hPAP) develop a cross-reactive immune response to the rat homologue (rPAP). We are currently investigating a plasmid DNA-based vaccine targeting prostatic acid phosphatase. Here, we investigate the mechanism behind the ability of the DNA vaccine to elicit a cross-reactive immune response by identifying epitopes of PAP recognized by T cells. Our working hypothesis is that immunization with a xenoantigen will result in the recognition of immunodominant epitope(s) of human PAP that are recognized by T cells with a cross-reactive response to the corresponding rat epitopes. To test this hypothesis, Lewis rats were immunized intradermally with a DNA vaccine encoding human PAP. Using a PAP peptide library, PAP-specific epitopes recognized by T cells in the Lewis rat model were mapped. PAP-specific T cell proliferation and interferon gamma production indicated two major immunogenic peptides of human PAP were recognized after immunization with hPAP DNA vaccine. However, the corresponding rat PAP peptides were not recognized. Rats immunized with these hPAP immunogenic peptides developed an immune response to the peptides and to the human PAP protein as determined by PAP-specific and peptide-specific T cell proliferation. These studies confirm that these peptides comprise naturally presented epitopes of hPAP. Overall, immunization with a DNA vaccine encoding a xenoantigen biases the immune response towards the foreign protein thus potentially limiting the cross-reactive response to the autoantigen.