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Identification of prostatic acid phosphatase (PAP) specific HLA-DR1-restricted T-cell epitopes.
- Source :
-
The Prostate [Prostate] 2012 May 15; Vol. 72 (7), pp. 730-40. Date of Electronic Publication: 2011 Aug 30. - Publication Year :
- 2012
-
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.<br />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.<br />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.<br />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.<br /> (Published 2011 Wiley Periodicals, Inc.)
- Subjects :
- Acid Phosphatase
Amino Acid Sequence
Animals
CD4-Positive T-Lymphocytes immunology
Epitope Mapping
HLA-A2 Antigen immunology
Humans
Leukocytes, Mononuclear immunology
Male
Mice
Mice, Transgenic
Molecular Sequence Data
Prostatic Neoplasms immunology
Prostatic Neoplasms therapy
Vaccines, DNA immunology
Vaccines, DNA therapeutic use
Epitopes, T-Lymphocyte immunology
HLA-DR1 Antigen immunology
Prostate enzymology
Prostate immunology
Protein Tyrosine Phosphatases immunology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0045
- Volume :
- 72
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- The Prostate
- Publication Type :
- Academic Journal
- Accession number :
- 22529020
- Full Text :
- https://doi.org/10.1002/pros.21477