Identification of HLA-DRB1*1501-restricted T-cell epitopes from human prostatic acid phosphatase

Elena N. Klyushnenkova, Diana V. Kouiavskaia, James A. Kodak, Arthur Vandenbark, Richard B. Alexander

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

BACKGROUND. The crucial role of CD4 T-cells in anti-tumor immune response is widely recognized, yet the identification of HLA class II-restricted epitopes derived from tumor antigens has lagged behind compared to class I epitopes. This is particularly true for prostate cancer. Based on the hypothesis that successful cancer immunotherapy will likely resemble autoimmunity, we searched for the CD4 T-cell epitopes derived from prostatic proteins that are restricted by human leukocyte antigen (HLA)-DRB1*1501, an allele associated with granulomatous prostatitis (GP), a disease that may have an autoimmune etiology. One of the antigens implicated in the development of autoimmunity in the prostate is prostatic acid phosphatase (PAP), which is also considered a promising target for prostate cancer immunotherapy. METHODS. We immunized transgenic (tg) mice engineered to express HLA-DRB1*1501 with human PAP. A library of overlapping 20-mer peptides spanning the entire human PAP sequence was screened in vitro for T-cell recognition by proliferative and interferon (IFN)-γ enzyme-linked immunosorbent spot (ELISPOT) assays. RESULTS. We identified two 20-mer peptides, PAP (133-152), and PAP (173-192), that were immunogenic and naturally processed from whole PAP in HLA-DRB1*1501 tg mice. These peptides were also capable of stimulating CD4 T lymphocytes from HLA-DRB1*1501-positive patients with GP and normal donors. CONCLUSIONS. These peptides can be used for the design of a new generation of peptide-based vaccines against prostate cancer. The study can also be helpful in understanding the role of autoimmunity in the development of some forms of chronic prostatitis.

Original languageEnglish (US)
Pages (from-to)1019-1028
Number of pages10
JournalProstate
Volume67
Issue number10
DOIs
StatePublished - Jul 1 2007

Fingerprint

T-Lymphocyte Epitopes
HLA Antigens
Prostatitis
Autoimmunity
Prostatic Neoplasms
Peptides
T-Lymphocytes
Immunotherapy
Transgenic Mice
Epitopes
Subunit Vaccines
Neoplasm Antigens
Interferons
Libraries
prostatic acid phosphatase
Prostate
Neoplasms
Enzyme-Linked Immunosorbent Assay
Alleles
Tissue Donors

Keywords

  • CD4 T lymphocytes
  • DR2 transgenic mice
  • HLA-DR15
  • Prostate cancer
  • Prostatitis

ASJC Scopus subject areas

  • Urology

Cite this

Klyushnenkova, E. N., Kouiavskaia, D. V., Kodak, J. A., Vandenbark, A., & Alexander, R. B. (2007). Identification of HLA-DRB1*1501-restricted T-cell epitopes from human prostatic acid phosphatase. Prostate, 67(10), 1019-1028. https://doi.org/10.1002/pros.20575

Identification of HLA-DRB1*1501-restricted T-cell epitopes from human prostatic acid phosphatase. / Klyushnenkova, Elena N.; Kouiavskaia, Diana V.; Kodak, James A.; Vandenbark, Arthur; Alexander, Richard B.

In: Prostate, Vol. 67, No. 10, 01.07.2007, p. 1019-1028.

Research output: Contribution to journalArticle

Klyushnenkova, EN, Kouiavskaia, DV, Kodak, JA, Vandenbark, A & Alexander, RB 2007, 'Identification of HLA-DRB1*1501-restricted T-cell epitopes from human prostatic acid phosphatase', Prostate, vol. 67, no. 10, pp. 1019-1028. https://doi.org/10.1002/pros.20575
Klyushnenkova, Elena N. ; Kouiavskaia, Diana V. ; Kodak, James A. ; Vandenbark, Arthur ; Alexander, Richard B. / Identification of HLA-DRB1*1501-restricted T-cell epitopes from human prostatic acid phosphatase. In: Prostate. 2007 ; Vol. 67, No. 10. pp. 1019-1028.
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AU - Alexander, Richard B.

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N2 - BACKGROUND. The crucial role of CD4 T-cells in anti-tumor immune response is widely recognized, yet the identification of HLA class II-restricted epitopes derived from tumor antigens has lagged behind compared to class I epitopes. This is particularly true for prostate cancer. Based on the hypothesis that successful cancer immunotherapy will likely resemble autoimmunity, we searched for the CD4 T-cell epitopes derived from prostatic proteins that are restricted by human leukocyte antigen (HLA)-DRB1*1501, an allele associated with granulomatous prostatitis (GP), a disease that may have an autoimmune etiology. One of the antigens implicated in the development of autoimmunity in the prostate is prostatic acid phosphatase (PAP), which is also considered a promising target for prostate cancer immunotherapy. METHODS. We immunized transgenic (tg) mice engineered to express HLA-DRB1*1501 with human PAP. A library of overlapping 20-mer peptides spanning the entire human PAP sequence was screened in vitro for T-cell recognition by proliferative and interferon (IFN)-γ enzyme-linked immunosorbent spot (ELISPOT) assays. RESULTS. We identified two 20-mer peptides, PAP (133-152), and PAP (173-192), that were immunogenic and naturally processed from whole PAP in HLA-DRB1*1501 tg mice. These peptides were also capable of stimulating CD4 T lymphocytes from HLA-DRB1*1501-positive patients with GP and normal donors. CONCLUSIONS. These peptides can be used for the design of a new generation of peptide-based vaccines against prostate cancer. The study can also be helpful in understanding the role of autoimmunity in the development of some forms of chronic prostatitis.

AB - BACKGROUND. The crucial role of CD4 T-cells in anti-tumor immune response is widely recognized, yet the identification of HLA class II-restricted epitopes derived from tumor antigens has lagged behind compared to class I epitopes. This is particularly true for prostate cancer. Based on the hypothesis that successful cancer immunotherapy will likely resemble autoimmunity, we searched for the CD4 T-cell epitopes derived from prostatic proteins that are restricted by human leukocyte antigen (HLA)-DRB1*1501, an allele associated with granulomatous prostatitis (GP), a disease that may have an autoimmune etiology. One of the antigens implicated in the development of autoimmunity in the prostate is prostatic acid phosphatase (PAP), which is also considered a promising target for prostate cancer immunotherapy. METHODS. We immunized transgenic (tg) mice engineered to express HLA-DRB1*1501 with human PAP. A library of overlapping 20-mer peptides spanning the entire human PAP sequence was screened in vitro for T-cell recognition by proliferative and interferon (IFN)-γ enzyme-linked immunosorbent spot (ELISPOT) assays. RESULTS. We identified two 20-mer peptides, PAP (133-152), and PAP (173-192), that were immunogenic and naturally processed from whole PAP in HLA-DRB1*1501 tg mice. These peptides were also capable of stimulating CD4 T lymphocytes from HLA-DRB1*1501-positive patients with GP and normal donors. CONCLUSIONS. These peptides can be used for the design of a new generation of peptide-based vaccines against prostate cancer. The study can also be helpful in understanding the role of autoimmunity in the development of some forms of chronic prostatitis.

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