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 were generated using iterative stimulations of PBMC from a prostate cancer patient with an autologous IFN-γ-treated carcinoma cell line in the presence of IL-2. A CD8^- T cell line and TCR αβ⁺ T cell clone were isolated that secreted IFN-γ and TNF-α in response to autologous prostate cancer cells but not to aatologous fibroblasts or lymphoblastoid cells. However, these T cells recognized several normal and malignant prostate epithelial cell lines without evidence of shared classical HLA molecules. The T cell line and clone also recognized colon cancers, but not melanomas, sarcomas, or lymphomas, suggesting recognition of a shared epithelium-associated Ag presented by nonclassical MHC or MHC-like molecules. Although Ag recognition by T cells was inhibited by mAb against CD8 and the TCR complex (anti-TCR αβ, CD3, Vβ12), it was not inhibited by mAb directed against MHC class Ia or MHC class H molecules. Neither target expression of CD1 molecules nor HLA-G correlated with T cell recognition, but β₂-microglobulin expression was essential. Ag expression was diminished by brefeldin A, lactacystin, and cycloheximide, but not by chloroquine, consistent with an endogenous/cytosolic Ag processed through the classical class I pathway. These results suggest that prostate cancer and colon cancer cells can process and present a shared peptidic Ag to TCR αβ⁺ T cells via a nonclassical MHC I-like molecule yet to be defined.