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.
