Identification of T helper epitopes from prostatic acid phosphatase

Helper T cells (Th cells) play a central role in the initiation and mainten ance of immune responses, including antitumor immunity. The ability of Th c ells in murine models to maintain and enhance the cytolytic efficacy of CD8 + CTLs has led to a renewed interest in identifying human tumor antigens re cognized by Th cells. Prostatic acid phosphatase (PAP) is a prostate cancer -associated tumor antigen. A rodent model has demonstrated that PAP-specifi c CTLs can induce destructive prostatitis. Human MHC class I epitopes deriv ed 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 t hat might be used to elicit PAP-specific Th responses, ultimately in the co ntext of human vaccines targeting PAP, Using peripheral blood mononuclear c ells (PBMCs) from subjects with and without PAP-specific Th responses, we s creened a panel of 10 potential peptide epitopes for peptide-specific T-cel l proliferation. Pour peptides, p81-95, p199-213, p228-242, and p308-322, w ere identified for which peptide-specific T-cell proliferation occurred in the majority of patient PBMC samples that also exhibited PAP-specific T-cel l proliferation, PBMCs from patients with prostate cancer and without PAP-s pecific Th immunity were then cultured ill vitro with these four peptides, Peptide-specific T-cell lines could be generated from two of the four pepti des, p199-213 and p228-242, that also proliferated in response to PAP prote in stimulation. The ability of these two peptides to elicit PAP-specific Th responses suggests that they represent naturally processed PAP-specific MH C class II epitopes.