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

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: T Yasoshima, N Sato, K Hirata, K Kikuchi
• Journal: Cancer (Cancer) Vol. 75 Issue 6 Suppl Pg. 1484-9 (Mar 15 1995) ISSN: 0008-543X [Print] United States
• PMID: 7889479 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• HLA-A Antigens
• HLA-A31 antigen
• Interferon-gamma

Topics

• Antibodies, Monoclonal
• Carcinoma, Signet Ring Cell (immunology)
• Cytotoxicity Tests, Immunologic
• HLA-A Antigens (immunology)
• Humans
• Interferon-gamma (pharmacology)
• Stomach Neoplasms (immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Tumor Cells, Cultured