CDB20:0002680 CLEC2B — KLRF1
Experimentally validated in Human; Orthology-inferred in Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep
Title
Journal:; Year Published:
Abstract
Mutual activation of natural killer cells and monocytes mediated by NKp80-AICL interaction.
Nature immunology, 2006; PubMed, Homo sapiens CLEC2B — Homo sapiens KLRF1
ABSTRACT: Receptors encoded by the natural killer (NK) cell gene complex (such as NKG2D) govern the reactivity of NK cells. However, the function and ligand(s) of the NK cell gene complex-encoded human NK cell receptor NKp80 remain elusive. Here we demonstrate that NKp80 binds to the genetically linked 'orphan' receptor AICL, which, like NKp80, is absent from rodents. We defined AICL as a myeloid-specific activating receptor that is upregulated by Toll-like receptor stimulation. AICL-NKp80 interactions promoted NK cell-mediated cytolysis of malignant myeloid cells. In addition, during crosstalk between NK cells and monocytes, NKp80 stimulated the release of proinflammatory cytokines from both cell types. Thus, by specifically bridging NK cells and myeloid cells, NKp80-AICL interactions may contribute to the initiation and maintenance of immune responses at sites of inflammation.
Genetically coupled receptor-ligand pair NKp80-AICL enables autonomous control of human NK cell responses.
Blood, 2013; PubMed, Homo sapiens CLEC2B — Homo sapiens KLRF1
ABSTRACT: NKp80 is a C-type lectin-like receptor broadly expressed on human natural killer (NK) cells, triggering cytotoxicity via an atypical cytoplasmic hemi-immunoreceptor tyrosine-based activation motif. As with other lectin-like NK receptors, NKp80 is encoded in the natural killer gene complex, but unlike most of these, adjacent to its ligand, ie, activation-induced C-type lectin (AICL). The reasons for the tight genetic linkage of this receptor-ligand pair remain elusive. Previous studies showed that NKp80 augments NK cell responses toward malignant and nonmalignant myeloid cells. Here, we report that resting human NK cells not only express NKp80 but also contain intracellular stores of AICL colocalizing with the Golgi complex. Domain-swapping experiments revealed that intracellular localization of AICL is determined by its C-type lectin-like ectodomain. Exposure of NK cells to monokines associated with conversion into memorylike cells induces substantial AICL cell surface expression, whereas NKp80 is downregulated, and NK cells become refractory to NKp80-mediated stimulation. AICL on monokine-exposed NK cells elicits NKp80-dependent effector responses by autologous NK cells and, hence, renders monokine-activated NK cells susceptible to NKp80-mediated cytolysis. Altogether, our data report a previously unrecognized regulatory circuit enabling autonomous control of human NK cell responses via the NKp80-AICL axis.