Identification of T helper epitopes from prostatic acid phosphatase.
Helper T cells (Th cells) play a central role in the initiation and maintenance of immune responses, including antitumor immunity. The ability of Th cells in murine models to maintain and enhance the cytolytic efficacy of CD8+ CTLs has led to a renewed interest in identifying human tumor antigens recognized by Th cells. Prostatic acid phosphatase (PAP) is a prostate cancer-associated tumor antigen. A rodent model has demonstrated that PAP-specific CTLs can induce destructive prostatitis. Human MHC class I epitopes derived from PAP have been identified previously, and peptide-specific CTLs have been shown to be able to lyse an MHC-restricted prostate cancer cell line. In the current study, we sought to identify Th epitopes derived from PAP that might be used to elicit PAP-specific Th responses, ultimately in the context of human vaccines targeting PAP. Using peripheral blood mononuclear cells (PBMCs) from subjects with and without PAP-specific Th responses, we screened a panel of 10 potential peptide epitopes for peptide-specific T-cell proliferation. Four peptides, p81-95, p199-213, p228-242, and p308-322, were identified for which peptide-specific T-cell proliferation occurred in the majority of patient PBMC samples that also exhibited PAP-specific T-cell proliferation. PBMCs from patients with prostate cancer and without PAP-specific Th immunity were then cultured in vitro with these four peptides. Peptide-specific T-cell lines could be generated from two of the four peptides, p199-213 and p228-242, that also proliferated in response to PAP protein stimulation. The ability of these two peptides to elicit PAP-specific Th responses suggests that they represent naturally processed PAP-specific MHC class II epitopes.
McNeel
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DG
Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, Washington 98195, USA. dmcneel@u.washington.edu
Nguyen
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LD
Disis
M L
ML
D000135:Acid Phosphatase; D000595:Amino Acid Sequence; D019496:Cancer Vaccines / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000276:immunology; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases