HLA-A2-restricted T-cell epitopes specific for prostatic acid phosphatase

Brian M. Olson, Thomas P. Frye, Laura E. Johnson, Lawrence Fong, Keith L. Knutson, Mary L. Disis, Douglas G. McNeel

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Prostatic acid phosphatase (PAP) has been investigated as the target of several antigen-specific anti-prostate tumor vaccines. The goal of antigen-specific active immunotherapies targeting PAP would ideally be to elicit PAP-specific CD8+ effector T cells. The identification of PAP-specific CD8+ T-cell epitopes should provide a means of monitoring the immunological efficacy of vaccines targeting PAP, and these epitopes might themselves be developed as vaccine antigens. In the current report, we hypothesized that PAP-specific epitopes might be identified by direct identification of pre-existing CD8+ T cells specific for HLA-A2-restricted peptides derived from PAP in the blood of HLA-A2-expressing individuals. 11 nonamer peptides derived from the amino acid sequence of PAP were used as stimulator antigens in functional ELISPOT assays with peripheral blood mononuclear cells from 20 HLA-A2+ patients with prostate cancer or ten healthy blood donors. Peptide-specific T cells were frequently identified in both groups for three of the peptides, p18-26, p112-120, and p135-143. CD8+ T-cell clones specific for three peptides, p18-26, p112-120, and p299-307, confirmed that these are HLA-A2-restricted T-cell epitopes. Moreover, HLA-A2 transgenic mice immunized with a DNA vaccine encoding PAP developed epitope-specific responses for one or more of these three peptide epitopes. We propose that this method to first identify epitopes for which there are pre-existing epitope-specific T cells could be used to prioritize MHC class I-specific epitopes for other antigens. In addition, we propose that the epitopes identified here could be used to monitor immune responses in HLA-A2+ patients receiving vaccines targeting PAP to identify potentially therapeutic immune responses.

Original languageEnglish (US)
Pages (from-to)943-953
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume59
Issue number6
DOIs
StatePublished - Jun 1 2010

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Keywords

  • CTL
  • ELISPOT
  • Epitope
  • HLA-A2
  • Prostatic acid phosphatase (PAP)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

Olson, B. M., Frye, T. P., Johnson, L. E., Fong, L., Knutson, K. L., Disis, M. L., & McNeel, D. G. (2010). HLA-A2-restricted T-cell epitopes specific for prostatic acid phosphatase. Cancer Immunology, Immunotherapy, 59(6), 943-953. https://doi.org/10.1007/s00262-010-0820-6