Bone marrow allograft rejection mediated by a novel murine NK receptor, NKG2I.
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 approximately 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.
Koike
Junzo
J
Dept. of Molecular Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuoku, Chiba City, Chiba 260-8670, Japan.
Wakao
Hiroshi
H
Ishizuka
Yuko
Y
Sato
Taka-aki
TA
Hamaoki
Masaru
M
Seino
Ken-ichiro
K
Koseki
Haruhiko
H
Nakayama
Toshinori
T
Taniguchi
Masaru
M
D000595:Amino Acid Sequence; D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015723:Gene Library; D006084:Graft Rejection / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D008969:Molecular Sequence Data; D055655:NK Cell Lectin-Like Receptor Subfamily K; D051381:Rats; D011916:Rats, Inbred F344; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D055607:Receptors, Natural Killer Cell; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous
C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell