Serine proteinase inhibitor 9 can be recognized by cytotoxic T lymphocytes of epithelial cancer patients.
Serine proteinase inhibitor 9 (PI-9) inhibits granzyme B-mediated apoptosis and interleukin-1beta-converting enzyme activity. In this study, we report that the PI-9 gene encodes antigenic epitopes recognized by the HLA-A24-restricted and tumor-reactive cytotoxic T lymphocytes (CTLs) of epithelial cancer patients. Screening of an autologous cDNA library using a CTL line recognizing HLA-A24+ tumor cells resulted in the isolation of a cDNA, which had an identical coding region to the previously described PI-9 genes. PI-9 gene was expressed in approximately three-fourths of epithelial cancer cell lines and all leukemic cell lines tested. It was also expressed in normal peripheral blood mononuclear cells (PBMCs), but not in a normal fibroblast cell line. CTL sublines contained T cells capable of recognizing the PI-9(292-300) and PI-9(348-356) peptides among 13 different peptides having the HLA-A24 binding motifs. These two peptides were recognized by the CTL line in a dose-dependent and HLA class-I-restricted manner, and also possessed the ability to induce HLA class I-restricted and tumor-reactive CTLs in PBMCs from HLA-A24+ cancer patients. These results demonstrate that PI-9 is recognized by HLA class I-restricted and tumor-reactive CTLs of epithelial cancer patients.
Tanaka
Koji
K
Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan. shichijo@med.kurume-u.ac.jp
Harashima
Nanae
N
Niiya
Fumihiko
F
Miyagi
Yoshiaki
Y
Hida
Naoya
N
Ochi
Mika
M
Imai
Nobue
N
Harada
Mamoru
M
Itoh
Kyogo
K
Shichijo
Shigeki
S
D001483:Base Sequence; D003001:Cloning, Molecular; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens / Q000032:analysis; D059871:HLA-A24 Antigen; D006801:Humans; D008969:Molecular Sequence Data; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology*; D015843:Serpins / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; C102316:SERPINB9 protein, human; D015843:Serpins