Natural cytotoxicity receptors and their ligands

Kruse, Philip H.; Matta, Jessica; Ugolini, Sophie; Vivier, Éric

doi:10.1038/icb.2013.98

Cited by 220 publications

(237 citation statements)

References 99 publications

(155 reference statements)

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“…and the inhibitory receptor NKG2A (62)(63)(64). Results from our microassays indicated that the ChAT + NK cells had no increase of cytolytic activity, which was confirmed in vitro by a cytotoxic assay of YAC-1 cells (Fig.…”

Section: Ly6cmentioning

confidence: 57%

Acetylcholine-producing NK cells attenuate CNS inflammation via modulation of infiltrating monocytes/macrophages

Jiang

Han

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The nonneural cholinergic system of immune cells is pivotal for the maintenance of immunological homeostasis. Here we demonstrate the expression of choline acetyltransferase (ChAT) and cholinergic enzymes in murine natural killer (NK) cells. Ly6Chi monocytes directly via the disruption of tolerance and inhibited the production of proinflammatory cytokines. Interestingly, ChAT + NK cells and CCR2 + Ly6C hi monocytes formed immune synapses; moreover, the impact of ChAT + NK cells was mediated by α7-nicotinic acetylcholine receptors. Finally, the NK cell cholinergic system up-regulated in response to autoimmune activation in multiple sclerosis, perhaps reflecting the severity of disease. Therefore, this study extends our understanding of the nonneural cholinergic system and the protective immune effect of acetylcholine-producing NK cells in autoimmune diseases.

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Section: Ly6cmentioning

confidence: 57%

Acetylcholine-producing NK cells attenuate CNS inflammation via modulation of infiltrating monocytes/macrophages

Jiang

Han

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…16-21 In spite of many efforts, so far, the panel of the NCR ligands has been only partially defined. 10,12,22 A reason of these difficulties is related to the fact that study models of receptor-ligand interaction for the NCR are rather limited, as only NKp46 is expressed also on NK cells of rat and mouse. Moreover, although the NCRs belong to the Ig superfamily, they greatly differ in their molecular structure, implying that their ligands may be rather heterogeneous.…”

Section: Introductionmentioning

confidence: 99%

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

et al. 2018

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The release of soluble ligands of activating Natural Killer (NK) cell receptors may represent a regulatory mechanism of NK cell function both in physiologic and in pathologic conditions. Here, we identified the extracellular matrix protein Nidogen-1 (NID1) as a ligand of NKp44, an important activating receptor expressed by activated NK cells. When released as soluble molecule, NID1 regulates NK cell function by modulating NKp44-induced IFN-γ production or cytotoxicity. In particular, it also modulates IFN-γ production induced by Platelet-Derived Growth Factor (PDGF)-DD following NKp44 engagement. We also show that NID1 may be present at the cell surface. In this form or when bound to a solid support (bNID1), NID1 fails to induce NK cell cytotoxicity or cytokine release. However, analysis by mass spectrometry revealed that exposure to bNID1 can induce in human NK cells relevant changes in the proteomic profiles suggesting an effect on different biological processes.

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“…Pattern recognition receptors, such as Toll-like receptors, c-type lectin, and natural cytotoxic receptors (NCRs), are germ line-encoded cell surface receptors that allow for spontaneous activation of effector cells of the innate immune system (23)(24)(25). FcγRs, in contrast, are responsible for bridging the innate and adaptive responses by providing an interface between innate immune cells and antigen-specific antibodies.…”

Section: Significancementioning

confidence: 99%

Optimal activation of Fc-mediated effector functions by influenza virus hemagglutinin antibodies requires two points of contact

Leon

Mullarkey

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

108

107

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Influenza virus strain-specific monoclonal antibodies (mAbs) provide protection independent of Fc gamma receptor (FcγR) engagement. In contrast, optimal in vivo protection achieved by broadly reactive mAbs requires Fc-FcγR engagement. Most strain-specific mAbs target the head domain of the viral hemagglutinin (HA), whereas broadly reactive mAbs typically recognize epitopes within the HA stalk. This observation has led to questions regarding the mechanism regulating the activation of Fc-dependent effector functions by broadly reactive antibodies. To dissect the molecular mechanism responsible for this dichotomy, we inserted the FLAG epitope into discrete locations on HAs. By characterizing the interactions of several FLAG-tagged HAs with a FLAG-specific antibody, we show that in addition to Fc-FcγR engagement mediated by the FLAG-specific antibody, a second intermolecular bridge between the receptor-binding region of the HA and sialic acid on effector cells is required for optimal activation. Inhibition of this second molecular bridge, through the use of an F(ab′) 2 or the mutation of the sialic acid-binding site, renders the Fc-FcγR interaction unable to optimally activate effector cells. Our findings indicate that broadly reactive mAbs require two molecular contacts to possibly stabilize the immunologic synapse and potently induce antibody-dependent cell-mediated antiviral responses: (i) the interaction between the Fc of a mAb bound to HA with the FcγR of the effector cell and (ii) the interaction between the HA and its sialic acid receptor on the effector cell. This concept might be broadly applicable for protective antibody responses to viral pathogens that have suitable receptors on effector cells. hemagglutinin | influenza virus | antibody-dependent cell-mediated immunity | broadly reactive antibodies | Fcγ receptor

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Natural cytotoxicity receptors and their ligands

Cited by 220 publications

References 99 publications

Acetylcholine-producing NK cells attenuate CNS inflammation via modulation of infiltrating monocytes/macrophages

Acetylcholine-producing NK cells attenuate CNS inflammation via modulation of infiltrating monocytes/macrophages

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

Optimal activation of Fc-mediated effector functions by influenza virus hemagglutinin antibodies requires two points of contact

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