Recent human tumor immunology research has identified several genes coding immunogenic peptides recognized by cytotoxic T lymphocytes (CTL) in melanoma tumors. However, such peptides in tumors of epithelial cell origins with clinically high incidence, such as stomach, colon, lung, etc., have not yet been determined. In this paper we describe a human leukocyte antigen (HLA)-A31 (A*31012)-restricted natural antigenic peptide recognized by the CTL clone, TcHST-2, of gastric signet ring cell carcinoma HST-2. This peptide was designated F4.2, and was composed of ten amino acid residues with two anchor motif residues necessary for binding to HLA-A31 molecules. The synthetic F4.2 peptide could enhance the reactivity of TcHST-2 against HST-2 cells. Furthermore, introduction of a minigene coding F4.2 peptide to HLA-A31 (+) HOBC8-A31-12 cells conferred cytotoxic susceptibility on the cells to TcHST-2. Some of the HLA-A31 gene-introduced stomach cancer lines, such as MKN28-A31-2, were lysed by TcHST-2, suggesting the presence of F4.2 peptide in at least some HLA-A31 (+) stomach cancers. Using immunoprecipitates made with cell lysates of MKN28-A31-2 and anti-HLA-A31 specific monoclonal antibody (mAb) 2D12 as well as mass spectrometry, it was indicated that this peptide may be expressed in MKN28-A31-2 cells. Our studies suggested that F4.2 peptide may act as the immunogenic peptide in HLA-A31 (+) stomach cancer patients.
|Gann Monographs on Cancer Research
|Published - 1999
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