We earlier found that a rat monoclonal antibody (mAb) RE2 can induce rapid death of murine activated, but not resting, lymphocytes and lymphocyte cell lines, in a complement-independent manner, a cell death differing from typical apoptosis or necrosis. We here found that this cell death is independent of pathways involving Fas, caspase, and phosphoinositide-3 kinase. With the advantage of producing human B cell line transfectants with stable expression of human/mouse xeno-chimeric MHC class I genes, we found that RE2 epitope resides on the murine class I α2 domain. However, the α3 domain plays a key role in transducing the death signal, which mediates extensive aggregation of the MHC class I-integrin-actin filament system, giving rise to membrane blebs and pores. In mouse models with T/NKT cell activation-associated fulminant hepatitis, administration of mAb RE2 almost completely inhibited the development of liver cell injuries. Taken collectively, this form of cell death may be involved in homeostatic immune regulation, and induction of this form of cell death using the mAbs may be potentially therapeutic for subjects with immunological diseases mediated by activated lymphocytes.
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4 August 2003
Brief Definitive Report|
July 28 2003
A Monoclonal Antibody to the α2 Domain of Murine Major Histocompatibility Complex Class I that Specifically Kills Activated Lymphocytes and Blocks Liver Damage in the Concanavalin A Hepatitis Model
Shuji Matsuoka,
Shuji Matsuoka
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
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Hiromichi Tsurui,
Hiromichi Tsurui
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
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Masaaki Abe,
Masaaki Abe
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
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Kazuo Terashima,
Kazuo Terashima
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
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Kazuhiro Nakamura,
Kazuhiro Nakamura
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
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Yoshitomo Hamano,
Yoshitomo Hamano
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
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Mareki Ohtsuji,
Mareki Ohtsuji
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
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Nakayuki Honma,
Nakayuki Honma
2Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Takasaki-shi 370-1295, Japan
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Isao Serizawa,
Isao Serizawa
2Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Takasaki-shi 370-1295, Japan
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Yasuyuki Ishii,
Yasuyuki Ishii
3Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, Ministry of Economic Trade and Industry, Osaka 564-8577, Japan
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Masafumi Takiguchi,
Masafumi Takiguchi
4Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto 862-0976, Japan
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Sachiko Hirose,
Sachiko Hirose
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
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Toshikazu Shirai
Toshikazu Shirai
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
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Shuji Matsuoka
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Hiromichi Tsurui
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Masaaki Abe
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Kazuo Terashima
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Kazuhiro Nakamura
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Yoshitomo Hamano
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Mareki Ohtsuji
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Nakayuki Honma
2Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Takasaki-shi 370-1295, Japan
Isao Serizawa
2Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Takasaki-shi 370-1295, Japan
Yasuyuki Ishii
3Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, Ministry of Economic Trade and Industry, Osaka 564-8577, Japan
Masafumi Takiguchi
4Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto 862-0976, Japan
Sachiko Hirose
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Toshikazu Shirai
1Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
Address correspondence to Dr. Toshikazu Shirai, Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. Phone: 81-3-5802-1038; Fax: 81-3-3813-3164; email: [email protected]
Received:
July 31 2002
Accepted:
June 08 2003
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2003
J Exp Med (2003) 198 (3): 497–503.
Article history
Received:
July 31 2002
Accepted:
June 08 2003
Citation
Shuji Matsuoka, Hiromichi Tsurui, Masaaki Abe, Kazuo Terashima, Kazuhiro Nakamura, Yoshitomo Hamano, Mareki Ohtsuji, Nakayuki Honma, Isao Serizawa, Yasuyuki Ishii, Masafumi Takiguchi, Sachiko Hirose, Toshikazu Shirai; A Monoclonal Antibody to the α2 Domain of Murine Major Histocompatibility Complex Class I that Specifically Kills Activated Lymphocytes and Blocks Liver Damage in the Concanavalin A Hepatitis Model . J Exp Med 4 August 2003; 198 (3): 497–503. doi: https://doi.org/10.1084/jem.20021301
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