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Recognition of a Shared Human Prostate Cancer-Associated Antigen by Nonclassical MHC-Restricted CD8⁺ T Cells

Franck Housseau^*, Robert K. Bright^1,*, Toni Simonis, Michael I. Nishimura^* and Suzanne L. Topalian^2,*

^* Surgery Branch, National Cancer Institute, and HLA Laboratory, Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892

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--treated carcinoma cell line in the presence of IL-2. A CD8⁺ T cell line and TCR ß⁺ T cell clone were isolated that secreted IFN- and TNF- in response to autologous prostate cancer cells but not to autologous 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 ß, CD3, Vß12), 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 ß₂-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 ß⁺ T cells via a nonclassical MHC I-like molecule yet to be defined.

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