The mechanism of human autologous gastric signet ring cell tumor rejection by cytotoxic T lymphocytes in the possible context of HLA-A31 molecule.

Abstract

Tumor rejection antigens in human melanomas, which are recognized by cytotoxic T lymphocytes (CTLs), have recently been identified. To elucidate the cytotoxic mechanism in tumors other than melanoma, several pairs of CTLs and tumor lines were established. The authors report that HLA-A31 may present a tumor rejection antigen that is recognized by the human autologous gastric signet ring cell carcinoma-specific CTL. They also briefly describe the in vitro enhancing effect of interferon-gamma (INF-gamma) on the lysis of tumor cells by autologous CTL. The MHC Class I-restricted CTL clone, TcHST-2, and autologous gastric signet ring cell carcinoma line, HST-2, were established. Cytotoxicity blocking assays of antibodies reacting against the MHC Class I nonpolymorphic determinant and HLA-A, B, and C haplotype elements, which are expressed on the HST-2 cells, were performed. Lysis of the autologous tumor cells (HST-2) by the CTL clone (TcHST-2) was enhanced when the tumor cells were pretreated with IFN-gamma. This lysis was selectively inhibited by the anti-nonpolymorphic MHC Class I determinant monoclonal antibody (MoAb) and anti-HLA-A31 haplotype-specific MoAb. However, TcHST-2 clone was not cytotoxic to HLA-A31+ allogeneic leukemia lines. Pretreatment of target cells with IFN-gamma may be a necessary procedure for the efficient lysis of HST-2 cells by autologous TcHST-2 CTL. The data indicate that TcHST-2 was MHC Class I-restricted HST-2 tumor-specific CTL and suggest that the HLA-A31 haplotype element is an antigen-presenting molecule. Also discussed is the nature of the antigenic peptides in gastric signet ring cell carcinoma.