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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
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 independe...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194093/ https://www.ncbi.nlm.nih.gov/pubmed/12885869 http://dx.doi.org/10.1084/jem.20021301 |
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author | Matsuoka, Shuji Tsurui, Hiromichi Abe, Masaaki Terashima, Kazuo Nakamura, Kazuhiro Hamano, Yoshitomo Ohtsuji, Mareki Honma, Nakayuki Serizawa, Isao Ishii, Yasuyuki Takiguchi, Masafumi Hirose, Sachiko Shirai, Toshikazu |
author_facet | Matsuoka, Shuji Tsurui, Hiromichi Abe, Masaaki Terashima, Kazuo Nakamura, Kazuhiro Hamano, Yoshitomo Ohtsuji, Mareki Honma, Nakayuki Serizawa, Isao Ishii, Yasuyuki Takiguchi, Masafumi Hirose, Sachiko Shirai, Toshikazu |
author_sort | Matsuoka, Shuji |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2194093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21940932008-04-11 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 Matsuoka, Shuji Tsurui, Hiromichi Abe, Masaaki Terashima, Kazuo Nakamura, Kazuhiro Hamano, Yoshitomo Ohtsuji, Mareki Honma, Nakayuki Serizawa, Isao Ishii, Yasuyuki Takiguchi, Masafumi Hirose, Sachiko Shirai, Toshikazu J Exp Med Brief Definitive Report 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. The Rockefeller University Press 2003-08-04 /pmc/articles/PMC2194093/ /pubmed/12885869 http://dx.doi.org/10.1084/jem.20021301 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Brief Definitive Report Matsuoka, Shuji Tsurui, Hiromichi Abe, Masaaki Terashima, Kazuo Nakamura, Kazuhiro Hamano, Yoshitomo Ohtsuji, Mareki Honma, Nakayuki Serizawa, Isao Ishii, Yasuyuki Takiguchi, Masafumi Hirose, Sachiko Shirai, Toshikazu 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2194093/ https://www.ncbi.nlm.nih.gov/pubmed/12885869 http://dx.doi.org/10.1084/jem.20021301 |
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