Tumor-associated antigen human chorionic gonadotropin beta contains numerous antigenic determinants recognized by in vitro-induced CD8+ and CD4+ T lymphocytes

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Abstract
The beta subunit of human chorionic gonadotropin (hCGβ) is markedly overexpressed by neoplastic cells of differing histological origin including those present in colon, breast, prostate and bladder tumors. We have previously shown that some patients with hCGβ-producing urothelial tumors have circulating T cells that proliferate in response to hCGβ. To make a comprehensive study of hCGβ as a potential target for cancer immunotherapy, we investigated whether hCGβ peptides could induce CD4+ or CD8+ T-cell responses in vitro. By stimulating peripheral blood mononuclear cells (PBMCs) from three donors with mixtures of overlapping 16-mer synthetic peptides analogous to portions of either the hCGβ20–71 or the hCGβ102–129 region, we established six CD4+ T-cell lines that proliferated specifically in response to five distinct determinants located within these two hCGβ regions. Three antigenic determinants (hCGβ52–67, 106–121 and 114–125) were presented by HLA-DR molecules, while the two other antigenic determinants (hCGβ48–63 and 56–67) were presented by HLA-DQ molecules. Interestingly, one T-cell line specific for peptide hCGβ106–121 recognized hCGβ peptides comprising, at position 117, either an alanine or an aspartic acid residue, with the latter residue being present within the protein expressed by some tumor cells. In addition, three other hCGβ-derived peptides that exhibited HLA-A*0201 binding ability were able to stimulate CD8+ cytotoxic T cells from two HLA-A*0201 donors. These three immunogenic peptides corresponded to regions hCGβ40–48, hCGβ44–52 and hCGβ75–84. Our results indicate that the tumor-associated antigen hCGβ possesses numerous antigenic determinants liable to stimulate CD4+ and CD8+ T lymphocytes, and might thus be an effective target antigen for the immunotherapy of hCGβ-producing tumors.

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