Identification of prostatic acid phosphatase (PAP) specific HLA-DR1-restricted T-cell epitopes.

Abstract

BACKGROUND Prostatic acid phosphatase (PAP) is a prostate cancer tumor antigen and is an immunological target in several active immunotherapy clinical trials for the treatment of prostate cancer. We and others have demonstrated that PAP-specific T-cell responses can be elicited and augmented following antigen-specific immunization in both humans and animal models. We have previously reported that prostate cancer patients immunized with a DNA vaccine encoding PAP (pTVG-HP) developed both CD4+ and CD8+ T-cell responses. PAP-specific, CD4+ T-cell proliferative responses were generated in three out of four HLA-DRB1*0101 patients suggesting the possibility that DR1-restricted epitopes exist. METHODS To identify PAP-specific HLA-DRB1*0101 restricted epitopes, we immunized HLA-A2.01/HLA-DRB1*0101 (A2/DR1) transgenic mice with the pTVG-HP DNA vaccine. To map DRB1*0101-restricted epitopes, splenocytes from immunized mice were screened against a library of overlapping 15-residue, PAP-derived peptides using an IFNγ ELISPOT assay. RESULTS We identified four HLA-DRB1*0101 epitopes for PAP in A2/DR1 mice (PAP(161-175) , PAP(181-195) , PAP(191-205) , and PAP (351-365) ). T cells specific for one epitope (PAP(181-195) ) were found to be augmented after immunization in a HLA-DRB1*0101+ prostate cancer patient. CONCLUSIONS The identification of MHC class II epitopes may provide tools to directly monitor immune responses after vaccination and may be important for the design of future prostate cancer vaccines.

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