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

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Abstract

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-γ 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.

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Koike, J., Wakao, H., Ishizuka, Y., Sato, T. A., Hamaoki, M., Seino, K. I., … Taniguchi, M. (2004). Bone Marrow Allograft Rejection Mediated by a Novel Murine NK Receptor, NKG2I. Journal of Experimental Medicine, 199(1), 137–143. https://doi.org/10.1084/jem.20030851

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