Cancer Immunology, Immunotherapy

, Volume 59, Issue 6, pp 943–953 | Cite as

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. McNeelEmail author
Original Article


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.


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



This work was supported for BMO, TPF, LEJ and DGM by NIH (K23 RR16489) and the US Army Medical Research and Materiel Command (DAMD 17-03-1-0050 and W81XWH-07-1-0038). This work was supported for KLK and MLD by grants from the NIH (K24 CA85218 and R01 CA75163), and for LF by R01 CA136753.


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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
    Email author
  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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