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

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 ‫ف‬ 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-␥ 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.

Role of Natural Killer Cell Subsets in Cardiac Allograft Rejection

“…Compared to inhibitory receptors, NK cell activating receptors on the whole are less well characterized, thus the receptor-ligand pair that triggers NK cell rejection of cardiac allografts may be difficult to identify. It has recently been reported that KLRE-1 (NKG2I) is required for NK cell rejection of H-2 d bone marrow transplants (36). While the ligand for NKG2I remains unknown, it may play a role in cardiac rejection.…”

Role of a NK receptor, KLRE-1, in bone marrow allograft rejection: analysis with KLRE-1–deficient mice

“…Splenic NK, spleen, bone marrow, and liver mononuclear cells were separated and stained with the appropriate antibodies as described 13,15 ; phycoerythrin (PE)-anti-DX5, cyanin 5 (Cy5)-anti-T-cell receptor ␤ (TCR␤), Cy5-anti-CD3⑀ (PharMingen, San Jose, CA), and Cy-5-labeled antibody against KLRE-1 (anti-NKG2I: 7E8) were used. 13 …”

“…KLRE-1 genomic clone was isolated from a mouse genomic library using the KLRE-1 cDNA as a probe (cDNA sequence, first described by Koike et al 13 ). The genomic DNA fragment from NsiI site located at 1.5 kb upstream of the exon 2 (which contains ATG for first methionine) to BglII site present at 5.0 kb downstream of the exon 2 was used to construct the targeting vector ( Figure 1A).…”

“…5,[7][8][9][10] Recently, a novel NK receptor, KLRE-1 (also known as NKG2I), belonging to the killer cell lectinlike receptors (KLRs) family has been characterized. [11][12][13] A series of experiments using anti-KLRE-1 mAbs indicate that this receptor plays a role in the cytotoxicity mediated by NK cells in vitro. 12,13 However, the definitive assessment for the functions of KLRE-1 has to await KLRE-1-deficient mice.…”

“…[11][12][13] A series of experiments using anti-KLRE-1 mAbs indicate that this receptor plays a role in the cytotoxicity mediated by NK cells in vitro. 12,13 However, the definitive assessment for the functions of KLRE-1 has to await KLRE-1-deficient mice.…”