Recognition of a shared human prostate cancer-associated antigen by nonclassical MHC-restricted CD8+T cells

To identify prostate cancer-associated Ags, tumor-reactive T lymphocytes we re generated using iterative stimulations of PBMC from a prostate cancer pa tient with an autologous IFN-gamma-treated carcinoma cell Line in the prese nce of IL-2, A CD8(+) T cell line and TCR alpha beta(+) T cell clone were i solated that secreted IFN-gamma and TNF-alpha in response to autologous pro state cancer cells but not to autologous fibroblasts or lymphoblastoid cell s, However, these T cells recognized several normal and malignant prostate epithelial cell lines without evidence of shared classical HLA molecules, T he T cell line and clone also recognized colon cancers, but not melanomas, sarcomas, or lymphomas, suggesting recognition of a shared epithelium-assoc iated Ag presented by nonclassical MHC or MHC-like molecules, Although Ag r ecognition by T cells was inhibited by mAb against CDS and the TCR complex (anti-TCR alpha beta, CD3, V beta 12), it was not inhibited by mAb directed against MHC class Ia or MHC class II molecules, Neither target expression of CD1 molecules nor HLA-G correlated with T cell recognition,but beta(2)-m icroglobulin expression was essential. Ag expression was diminished by bref eldin A, lactacystin, and cycloheximide, but not by chloroquine, consistent with an endogenous/cytosolic Ag processed through the classical class I pa thway. These results suggest that prostate cancer and colon cancer cells ca n process and present a shared peptidic Ag to TCR alpha beta(+) T cells via a nonclassical MHC I-like molecule yet to be defined.