This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by McNeel, D. G. Articles by Disis, M. L. Search for Related Content PubMed PubMed Citation Articles by McNeel, D. G. Articles by Disis, M. L.

Identification of T Helper Epitopes from Prostatic Acid Phosphatase¹

Department of Medicine, Division of Medical Oncology, University of Washington, Seattle, Washington 98195

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.

This article has been cited by other articles:

				G. Penna, S. Amuchastegui, C. Cossetti, F. Aquilano, R. Mariani, N. Giarratana, E. De Carli, B. Fibbi, and L. Adorini Spontaneous and Prostatic Steroid Binding Protein Peptide-Induced Autoimmune Prostatitis in the Nonobese Diabetic Mouse J. Immunol., August 1, 2007; 179(3): 1559 - 1567. [Abstract] [Full Text] [PDF]

				T. P.F. Gade, W. Hassen, E. Santos, G. Gunset, A. Saudemont, M. C. Gong, R. Brentjens, X.-S. Zhong, M. Stephan, J. Stefanski, et al. Targeted Elimination of Prostate Cancer by Genetically Directed Human T Lymphocytes Cancer Res., October 1, 2005; 65(19): 9080 - 9088. [Abstract] [Full Text] [PDF]

				R. Schroers, L. Shen, L. Rollins, C. M. Rooney, K. Slawin, G. Sonderstrup, X. F. Huang, and S.-Y. Chen Human Telomerase Reverse Transcriptase-Specific T-Helper Responses Induced by Promiscuous Major Histocompatibility Complex Class II-Restricted Epitopes Clin. Cancer Res., October 15, 2003; 9(13): 4743 - 4755. [Abstract] [Full Text] [PDF]

				R. Schroers, L. Shen, L. Rollins, Z. Xiao, G. Sonderstrup, K. Slawin, X. F. Huang, and S.-Y. Chen Identification of MHC Class II-restricted T-cell Epitopes in Prostate-specific Membrane Antigen Clin. Cancer Res., August 1, 2003; 9(9): 3260 - 3271. [Abstract] [Full Text] [PDF]