The Journal of Experimental Medicine
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Published 5 January 2004. doi:10.1084/jem.20030851
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 1, 137-144
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Brief Definitive Report

Bone Marrow Allograft Rejection Mediated by a Novel Murine NK Receptor, NKG2I

Junzo Koike1, Hiroshi Wakao3, Yuko Ishizuka3, Taka-aki Sato4, Masaru Hamaoki4, Ken-ichiro Seino3,5, Haruhiko Koseki3, Toshinori Nakayama2 and Masaru Taniguchi1,3

1 Department of Molecular Immunology, Graduate School of Medicine, Chiba University, Chiba City, Chiba 260-8670, Japan
2 Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba City, Chiba 260-8670, Japan
3 Institute of Physical and Chemical Research, Research Center for Allergy and Immunology, Yokohama City, Kanagawa 230-0045, Japan
4 Department of Diagnostics, YAMASA Corporation, Choshi, Chiba 288-0056, Japan
5 PRESTO, Japan Science and Technology Corporation, Saitama 332-0012, Japan

Address correspondence to Masaru Taniguchi, Dept. of Molecular Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoku, Chiba City, Chiba 260-8670, Japan. Phone: 81-43-226-2184; Fax: 81-43-227-1498; email: taniguti{at}med.m.chiba-u.ac.jp

Natural killer (NK) cells mediate bone marrow allograft rejection. However, the molecular mechanisms underlying such a rejection remain elusive. In previous analyses, it has been shown that NK cells recognize allogeneic target cells through Ly-49s and CD94/NKG2 heterodimers. Here, we describe identification and characterization of a novel murine NK receptor, NKG2I, belonging to the NKG2 family. NKG2I, which was composed of 226 amino acids, showed ~40% homology to the murine NKG2D and CD94 in the C-type lectin domain. Flow cytometric analysis with anti-NKG2I monoclonal antibody (mAb) revealed that expression of NKG2I was largely confined to NK and NKT cells, but was not seen in T cells. Furthermore, anti-NKG2I mAb inhibited NK cell–mediated cytotoxicity, whereas cross-linking of NKG2I enhanced interleukin 2– and interleukin 12–dependent interferon-{gamma} production. Similarly, the injection of anti-NKG2I mAb before the allogeneic bone marrow transfer in vivo impinged on the function of NKG2I, resulting in the enhanced colony formation in the spleen. NKG2I is a novel activating receptor mediating recognition and rejection of allogeneic target cells.

Key Words: C-type lectin family • NK cells • activating receptor • IFN-{gamma} • NKT cells


The online version of this article includes supplemental material.


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