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Prostate. 2012 May 15;72(7):730-40. doi: 10.1002/pros.21477. Epub 2011 Aug 30.

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

Author information

1
Department of Medicine, University of Wisconsin, Madison, Wisconsin 53705, USA.

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 IFN╬│ 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.

PMID:
22529020
DOI:
10.1002/pros.21477
[Indexed for MEDLINE]

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