Identification of antigenic epitopes recognized by Mac-2 binding protein-specific cytotoxic T lymphocytes in an HLA-A24 restricted manner.
We previously reported that 90K/Mac-2 binding protein (M2BP) is highly expressed in lung cancer and that M2BP-specific immunity was observed in many patients with lung cancer. These findings suggested the possibility of using M2BP as a target antigen in cancer immunotherapy. In this study, we selected 11 peptides derived from M2BP with an HLA-A24 binding motif and analyzed their ability to induce M2BP-specific cytotoxic T lymphocytes (CTL). CTLs were generated with the M2BP-derived peptides from peripheral blood CD8-positive T lymphocytes of HLA-A24-positive healthy donors in multiple in vitro stimulations. Two CTLs, one induced with M2BP(241-250) (GYCASLFAIL) and the other with M2BP(568-576) (GFRTVIRPF), produced interferon-gamma in response to HLA-A24-positive TISI cells pulsed with the same peptide used for the in vitro stimulation. Although the CTLs induced with M2BP(241-250) reacted with both peptide-pulsed TISI cells and BT20 cells expressing both M2BP and HLA-A24, the CTLs induced with M2BP(568-576) did not react with BT20 cells. The cytokine production was blocked by antibodies against HLA class I in CTLs induced using M2BP(241-250), but not in CTLs induced using M2BP(568-576). These findings suggest that M2BP(241-250) is naturally processed from the native M2BP molecule in cancer cells and recognized by M2BP-specific CTLs in an HLA-A24 restriction. An M2BP-derived CTL epitope with an HLA-A24 binding motif was identified for the first time in this study, and it is expected to be useful as a target antigenic epitope in clinical immunotherapy for lung cancer.
Kontani
Keiichi
K
Department of Surgery, Shiga University of Medical Science, Seta-tsukinowa, Otsu 520-2192, Japan. konbat@med.kagawa-u.ac.jp
Teramoto
Koji
K
Ozaki
Yoshitomo
Y
Fujita
Takuya
T
Tezuka
Noriaki
N
Sawai
Satoru
S
Watanabe
Hiroyoshi
H
Fujino
Shozo
S
Yokomise
Hiroyasu
H
Ohkubo
Iwao
I
D001943:Breast Neoplasms / Q000473:pathology; D002277:Carcinoma / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D000939:Epitopes; D005260:Female; D037502:Galectin 3 / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D016207:Cytokines; D000939:Epitopes; D037502:Galectin 3; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen