The Journal of Experimental Medicine
CSHL Meetings & Courses
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 28 July 2003 doi:10.1084/jem.20021301
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Matsuoka, S.
Right arrow Articles by Shirai, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Matsuoka, S.
Right arrow Articles by Shirai, T.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© Rockefeller University Press, 0022-1007/2003/8/497 $5.00
The Journal of Experimental Medicine, Volume 198, Number 3, 497-503

Brief Definitive Report

 A Monoclonal Antibody to the {alpha}2 Domain of Murine Major Histocompatibility Complex Class I that Specifically Kills Activated Lymphocytes and Blocks Liver Damage in the Concanavalin A Hepatitis Model

Shuji Matsuoka1, Hiromichi Tsurui1, Masaaki Abe1, Kazuo Terashima1, Kazuhiro Nakamura1, Yoshitomo Hamano1, Mareki Ohtsuji1, Nakayuki Honma2, Isao Serizawa2, Yasuyuki Ishii3, Masafumi Takiguchi4, Sachiko Hirose1 and Toshikazu Shirai1

1 Department of Pathology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan
2 Pharmaceutical Research Laboratory, Kirin Brewery Co., Ltd., Takasaki-shi 370-1295, Japan
3 Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology, Ministry of Economic Trade and Industry, Osaka 564-8577, Japan
4 Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto 862-0976, 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: toshirai{at}med.juntendo.ac.jp

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 {alpha}2 domain. However, the {alpha}3 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.

Key Words: adhesion molecule • cell death • cytoskeleton • immunotherapy • MHC class I


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS