title: Recognition of prostate-specific antigenic peptide determinants by human CD4 and CD8 T cells.
abstract: It is now becoming accepted that one is not tolerant to all the determinants of self proteins: the T cell repertoire directed to some sequences in self proteins is intact and can be activated. When a self protein is exclusively expressed by tumour cells, the T cell repertoire directed to the particular self antigen can potentially be activated to attack the tumour: this would amount to induction of a beneficial autoimmune response. Prostate cancer offers a unique opportunity for activation of a tumour-specific immune response owing to the exclusive synthesis of prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) by prostatic tissue and prostate tumour cells. In this study we examine the CD4 and CD8 T cell repertoires specific for peptides of PSA and PSM in normal human male individuals, using short-term, peptide antigen-driven CD4 and CD8 T cell lines. We show that short-term, CD4 T cell lines derived from six HLA-DR4 individuals showed strong proliferative responses to six of 10 tested peptides of PSA, selected as to contain a DR4 binding motif. Short-term, CD8 T cell lines from three HLA-A1 individuals showed specific cytolytic activity for autologous targets loaded with five of five tested peptides of PSA and PSM, selected to possess an HLA-A1 binding motif. One of the peptides chosen is termed a 'dual-motif' peptide, as it encodes determinants for both CD4 and CD8 T cells. These results, indicating the existence of CD4 and CD8 T cells against determinants of the self proteins, PSA and PSM, in healthy male individuals reveal the potential of the T cell repertoire from the typical prostate cancer patient to eradicate prostate tumours upon being appropriately activated.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California, Los Angeles, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Corman
authors.forename: E E
authors.initials: EE
authors.lastname: Sercarz
authors.forename: N K
authors.initials: NK
authors.lastname: Nanda
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000954:Antigens, Surface; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002268:Carboxypeptidases / Q000276:immunology*; D002478:Cells, Cultured; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D043425:Glutamate Carboxypeptidase II; D015804:HLA-DR4 Antigen / Q000276:immunology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017430:Prostate-Specific Antigen / Q000276:immunology*
chemical_list: D000954:Antigens, Surface; D018984:Epitopes, T-Lymphocyte; D015804:HLA-DR4 Antigen; D002268:Carboxypeptidases; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen