Cancer Immunology, Immunotherapy

, Volume 59, Issue 6, pp 943–953

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
Original Article

DOI: 10.1007/s00262-010-0820-6

Cite this article as:
Olson, B.M., Frye, T.P., Johnson, L.E. et al. Cancer Immunol Immunother (2010) 59: 943. doi:10.1007/s00262-010-0820-6

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.

Keywords

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

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Brian M. Olson
    • 1
  • Thomas P. Frye
    • 1
  • Laura E. Johnson
    • 1
  • Lawrence Fong
    • 2
  • Keith L. Knutson
    • 3
  • Mary L. Disis
    • 4
  • Douglas G. McNeel
    • 1
    • 5
  1. 1.Department of MedicineUniversity of WisconsinMadisonUSA
  2. 2.Division of Hematology/OncologyUniversity of CaliforniaSan FranciscoUSA
  3. 3.Department of ImmunologyMayo ClinicRochesterUSA
  4. 4.Tumor Vaccine Group, Division of Medical OncologyUniversity of WashingtonSeattleUSA
  5. 5.Wisconsin Institutes for Medical ResearchUniversity of Wisconsin Paul P. Carbone Comprehensive Cancer CenterMadisonUSA

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