Identification of HLA-DRB1*1501-restricted T-cell epitopes from prostate-specific antigen

Elena N. Klyushnenkova, Jason Link, Warren T. Oberle, James Kodak, Cathleen Rich, Arthur Vandenbark, Richard B. Alexander

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The development of immunotherapy for prostate cancer based on the induction of autoimmunity to prostate tissue is very attractive because prostate is not a vital organ beyond the reproductive years. CD4 Tcells play an important role in the development of antitumor immune responses, yet the identification of naturally processed MHC Class II - restricted epitopes derived from prostate differentiation antigens has not been described. To facilitate the search for prostate-specific antigen (PSA)-derived MHC class II - restricted peptides, we immunized mice transgenic for HLA-DRB1*1501 with human PSA and showed a robust dose-dependent immune response to the antigen. Screening a library of overlapping 20-mer peptides that span the entire PSA sequence identified two 20-mer peptides, PSA171-190 and PSA221-240, which were responsible for this reactivity. Immunization of DR2b transgenic mice with these peptides induced specific responses to the peptide and whole PSA. Identified peptides were used to stimulate CD4 T cells from HLA-DRB1*1501+ patients with a rare condition, granulomatous prostatitis, and who seem to have a preexisting immune response directed against the prostate gland. We previously showed a linkage of granulomatous prostatitis to HLA-DRB1*1501, suggesting that this disease may have an autoimmune etiology. Peptide-specific CD4 T-cell lines were generated from the peripheral blood of these patients as well as one patient with prostate cancer. These lines also recognized whole, processed PSA in the context of HLA-DRB1*1501. This study will be instrumental in understanding the interaction between circulating self-reactive T cells, organ-specific autoimmunity, and antitumor immune response. The use of these peptides for the immunotherapy of prostate cancer is under investigation.

Original languageEnglish (US)
Pages (from-to)2853-2861
Number of pages9
JournalClinical Cancer Research
Volume11
Issue number8
DOIs
StatePublished - Apr 15 2005

Fingerprint

HLA-DRB1 Chains
T-Lymphocyte Epitopes
Prostate-Specific Antigen
Peptides
Prostate
Prostatic Neoplasms
Prostatitis
Autoimmunity
T-Lymphocytes
Immunotherapy
Transgenic Mice
Histocompatibility Antigens Class II
Differentiation Antigens
Libraries
Epitopes
Immunization
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Identification of HLA-DRB1*1501-restricted T-cell epitopes from prostate-specific antigen. / Klyushnenkova, Elena N.; Link, Jason; Oberle, Warren T.; Kodak, James; Rich, Cathleen; Vandenbark, Arthur; Alexander, Richard B.

In: Clinical Cancer Research, Vol. 11, No. 8, 15.04.2005, p. 2853-2861.

Research output: Contribution to journalArticle

Klyushnenkova, Elena N. ; Link, Jason ; Oberle, Warren T. ; Kodak, James ; Rich, Cathleen ; Vandenbark, Arthur ; Alexander, Richard B. / Identification of HLA-DRB1*1501-restricted T-cell epitopes from prostate-specific antigen. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 8. pp. 2853-2861.
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