Affinage

NCR3

Natural cytotoxicity triggering receptor 3 · UniProt O14931

Length
201 aa
Mass
21.6 kDa
Annotated
2026-04-29
100 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NKp30 (NCR3/CD337) is an activating natural cytotoxicity receptor of the immunoglobulin superfamily that couples innate immune recognition of tumor cells, pathogen-infected cells, and immature dendritic cells to NK cell cytotoxicity and cytokine secretion. NKp30 contains a single I-type Ig-like ectodomain that engages the tumor-associated ligand B7-H6 via both front and back β-sheets of its β-sandwich, the stress-induced ligand BAT3/BAG-6, and the inhibitory ligand galectin-3, while pathogen-derived proteins such as CMV pp65 and poxviral hemagglutinin subvert signaling by dissociating the CD3ζ adaptor chain or blocking receptor activation (PMID:10562324, PMID:19528259, PMID:21422170, PMID:18055229, PMID:15821739, PMID:25315772). Upon ligand engagement, NKp30 signals through associated CD3ζ and FcεRIγ adaptors to activate PI3K/Akt, Syk, Erk1/2, and canonical NF-κB pathways, triggering RAB27A-dependent degranulation and secretion of TNF-α, IFN-γ, and CC-chemokines, with N-glycosylation-dependent oligomerization and stalk-region contacts modulating ligand affinity and signaling output (PMID:11385609, PMID:18025182, PMID:17255357, PMID:32708305, PMID:22807449). NKp30 expression is transcriptionally suppressed by TGF-β1 and selectively maintained by IL-2, while its principal tumor ligand B7-H6 is regulated by Myc-driven transcription, HDAC-dependent chromatin remodeling, and ADAM-10/17-mediated ectodomain shedding, providing multiple layers of immune evasion and activation control (PMID:12646700, PMID:38698855, PMID:27622013, PMID:23801635, PMID:24780758).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 High

    Identification of NKp30 as a novel NK-specific activating receptor resolved how NK cells use non-MHC-restricted Ig-superfamily receptors coupled to CD3ζ ITAM signaling to trigger cytotoxicity.

    Evidence Monoclonal antibody screening, molecular cloning, redirected killing assays, and CD3ζ phosphorylation analysis in human NK cells

    PMID:10562324

    Open questions at the time
    • Cellular ligand(s) unidentified
    • Contribution of FcεRIγ adaptor not yet tested
    • In vivo relevance not established
  2. 2002 High

    Establishing NKp30 as the dominant receptor for NK killing of immature dendritic cells placed it at the interface of innate and adaptive immunity, showing NK cells edit the DC repertoire through NKp30.

    Evidence Blocking antibody experiments in NK–DC co-culture cytotoxicity assays

    PMID:11828009

    Open questions at the time
    • DC-expressed ligand for NKp30 unknown
    • Mechanism distinguishing immature from mature DC recognition unresolved
  3. 2005 High

    Dissection of NKp30 downstream signaling through PI3K/Akt and its dual cytotoxic/cytokine-secretory functions revealed that NKp30 activates both degranulation and TNFα/IFNγ production that drives DC maturation, with the cytokine arm operating independently of perforin.

    Evidence PI3K inhibitors (LY294002, wortmannin) in redirected killing and Akt phosphorylation assays; perforin-deficient NK cell analysis; cytokine neutralization in NK–DC co-cultures

    PMID:11385609 PMID:15784725

    Open questions at the time
    • Contribution of Syk, Erk, NF-κB pathways not yet mapped
    • Adaptor chain requirements beyond CD3ζ not defined
  4. 2005 High

    Discovery that CMV pp65 directly binds NKp30 and dissociates CD3ζ provided the first example of a viral immune evasion mechanism targeting an NCR at the adaptor-coupling level.

    Evidence Direct binding assays, co-immunoprecipitation, CD3ζ dissociation analysis, functional NK cytotoxicity assays

    PMID:15821739

    Open questions at the time
    • Structural basis of pp65–NKp30 interaction unknown
    • Whether other herpesviruses use analogous mechanisms untested
  5. 2007 High

    Identification of BAT3/BAG-6 as an NKp30 ligand released by tumor cells, and demonstration that RAB27A-dependent degranulation is selectively required for NKp30- but not CD16-mediated killing, defined both a tumor ligand and a unique granule-release pathway for this receptor.

    Evidence Co-IP and direct binding of BAT3 to NKp30 with in vivo tumor rejection model; patient NK cells from Griscelli syndrome (RAB27A mutations) in redirected killing assays with Vav1 phosphorylation analysis

    PMID:17255357 PMID:18055229

    Open questions at the time
    • BAT3 release mechanism from tumor cells not characterized
    • Whether BAT3 and the later-discovered B7-H6 compete for the same binding site unknown
  6. 2008 High

    Differential receptor engagement studies in decidual NK cells showed NKp30 preferentially triggers cytokine/chemokine secretion (IFNγ, TNFα, MIP-1α/β) whereas NKp46 triggers cytotoxicity, establishing tissue-specific functional specialization of NCRs.

    Evidence Receptor-specific mAb engagement with calcium mobilization, perforin polarization, and granule exocytosis readouts in decidual NK cells

    PMID:18713971

    Open questions at the time
    • Molecular basis for divergent signaling outcomes from NKp30 vs NKp46 despite shared CD3ζ usage unresolved
  7. 2009 High

    Discovery of B7-H6 as a tumor-restricted surface ligand for NKp30 provided the first defined activating ligand selectively expressed on transformed cells, establishing NKp30 as a bona fide tumor immunosurveillance receptor.

    Evidence Mass spectrometry identification, NKp30-Fc pulldown, direct binding assays, flow cytometry of normal versus tumor tissues

    PMID:19528259

    Open questions at the time
    • Structural basis of NKp30–B7-H6 interaction not yet determined
    • In vivo anti-tumor role in autologous setting not tested
  8. 2011 High

    Crystal structures of the NKp30–B7-H6 complex revealed an unconventional binding mode using both front and back β-sheets of the Ig domain, and downstream NF-κB pathway mapping via Syk identified how NKp30 signals activate transcription factors beyond PI3K.

    Evidence X-ray crystallography of NKp30 alone and in complex with B7-H6; IκB degradation, EMSA, NF-κB reporter assays with Syk inhibitor piceatannol

    PMID:18025182 PMID:21422170 PMID:21444796

    Open questions at the time
    • Whether oligomeric NKp30 binds B7-H6 differently from monomer unknown
    • Relative contributions of NF-κB vs PI3K vs Erk pathways to specific effector functions unresolved
  9. 2011 High

    Poxviral hemagglutinin was shown to bind NKp30 yet inhibit rather than activate NK function, demonstrating that ligand identity determines whether NKp30 engagement is activating or inhibitory—a second viral evasion strategy distinct from CMV pp65.

    Evidence NCR-CD3ζ reporter cells, siRNA-mediated NCR silencing, recombinant soluble HA binding, NK cytotoxicity assays

    PMID:21901096

    Open questions at the time
    • Structural basis distinguishing activating vs inhibitory ligand engagement unknown
  10. 2012 High

    Multiple studies established that N-glycosylation and the stalk region act as a molecular switch controlling NKp30 ligand affinity, while NKp30 accumulates at the immunological synapse and activates Erk1/2, broadening the known signaling repertoire.

    Evidence Mutagenesis of glycosylation sites with binding and signaling assays; confocal microscopy of NK–tumor synapses; Erk1/2 phosphorylation analysis

    PMID:22221078 PMID:22807449

    Open questions at the time
    • Which glycan structures at each site tune affinity not determined
    • Whether stalk-region flexibility differs between NKp30 isoforms untested
  11. 2013 High

    BAG-6 domain mapping showed that a C-terminal dimeric fragment binds NKp30 with high affinity yet inhibits signaling, while B7-H6 was found to be inducible on inflammatory monocytes/neutrophils and epigenetically regulated by HDACs, revealing that ligand availability is dynamically controlled.

    Evidence Recombinant BAG-6 domain mapping with biophysical KD measurement; flow cytometry of patient monocytes with TLR stimulation; ChIP and luciferase reporter assays for HDAC regulation of B7-H6 promoter

    PMID:23687088 PMID:23801635 PMID:24133212

    Open questions at the time
    • Whether soluble BAG-6 fragment is generated physiologically unknown
    • Full epigenetic landscape of B7-H6 regulation incomplete
  12. 2014 High

    Identification of galectin-3 as an inhibitory NKp30 ligand and ADAM-10/17 as B7-H6 sheddases defined two tumor immune evasion axes that reduce NKp30-mediated immunosurveillance.

    Evidence SPR for galectin-3–NKp30 binding with xenograft validation; pharmacological ADAM inhibitors and siRNA with surface B7-H6 measurement and NK activation assays

    PMID:24780758 PMID:25315772

    Open questions at the time
    • Whether galectin-3 and B7-H6 compete for the same NKp30 surface not tested
    • In vivo therapeutic potential of ADAM inhibition for NKp30-dependent immunity not assessed
  13. 2016 High

    Myc was identified as a direct transcriptional driver of B7-H6 expression, linking oncogene activation to NKp30 ligand upregulation and providing a mechanistic explanation for tumor-selective B7-H6 expression.

    Evidence ChIP showing Myc binding at B7-H6 promoter, luciferase reporter assays, c-Myc/N-Myc siRNA/shRNA and pharmacological inhibition with NK degranulation readout

    PMID:27622013

    Open questions at the time
    • Whether other oncogenic pathways also drive B7-H6 expression not comprehensively surveyed
    • Contribution of Myc vs HDAC regulation to B7-H6 levels in specific tumor types unresolved
  14. 2018 High

    FcεRIγ was shown to be an essential adaptor for NKp30 surface expression and function in IL-15-induced CD8+ T cells, requiring promoter demethylation, establishing that NKp30 function extends beyond NK cells through epigenetic reprogramming of adaptors.

    Evidence FcεRIγ knockdown/overexpression, promoter methylation analysis, flow cytometry, xenograft tumor model

    PMID:29895693

    Open questions at the time
    • Whether FcεRIγ is also limiting for NKp30 on NK cells unresolved
    • Signaling differences between CD3ζ- and FcεRIγ-coupled NKp30 not defined
  15. 2020 High

    Crystallography of glycosylated NKp30–B7-H6 complex demonstrated that N-glycans drive NKp30 dimerization, providing a structural basis for how glycosylation-dependent oligomerization tunes receptor sensitivity.

    Evidence X-ray crystallography of glycosylated complex, enzymatic deglycosylation with size-exclusion chromatography and binding affinity measurements

    PMID:32708305

    Open questions at the time
    • Whether glycan-dependent dimers form on live NK cell surfaces unresolved
    • Functional consequence of oligomerization for threshold signaling not directly tested in cells
  16. 2024 Medium

    IL-2 was identified as a selective regulator of NKp30 (but not NKp46) surface expression, and ectopic overexpression of immunostimulatory NKp30 isoforms rescued anti-tumor cytotoxicity independently of IL-2, revealing isoform-specific functional control.

    Evidence IL-2 deprivation assays comparing NKp30 and NKp46, NKp30a/b isoform overexpression, in vivo xenograft model

    PMID:38698855

    Open questions at the time
    • Mechanism by which IL-2 selectively controls NKp30 vs NKp46 unclear
    • Transcriptional vs post-transcriptional regulation of NKp30 isoform switching not fully characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how NKp30 discriminates activating from inhibitory ligands structurally, how glycan-dependent oligomerization on the live cell surface integrates with adaptor recruitment to set signaling thresholds, and the in vivo contributions of individual NKp30 splice variants to tumor immunosurveillance versus immunosuppression.
  • No structure of NKp30 bound to an inhibitory ligand (galectin-3, pp65, poxviral HA)
  • In vivo isoform-specific functions not delineated in genetic models
  • Relative stoichiometry of CD3ζ vs FcεRIγ in NKp30 complexes on different cell types unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 8 R-HSA-162582 Signal Transduction 3
Partners
B7-H6BAG6CD247FCER1GICAM1LGALS3

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 NKp30 (NCR3) is a 30-kD triggering receptor selectively expressed on all resting and activated human NK cells, belonging to the immunoglobulin superfamily with a single V-type domain and a charged residue in the transmembrane portion. It associates with CD3ζ chains that become tyrosine phosphorylated upon activation. Encoded by the previously identified 1C7 gene. Monoclonal antibody generation, molecular cloning, redirected killing assays, masking experiments, biochemical analysis of CD3ζ phosphorylation The Journal of experimental medicine High 10562324
2002 NKp30 is the major activating receptor mediating NK cell killing of immature dendritic cells (DCs). Both immature and mature DCs activate resting NK cells, but this DC-stimulating function uses an NKp30-independent mechanism, whereas killing of immature DCs is primarily NKp30-dependent. Monoclonal antibody masking, NK-DC co-culture cytotoxicity assays, NK cell activation assays The Journal of experimental medicine High 11828009
2001 NKp30 does not recognize viral hemagglutinins (influenza HA or Sendai virus HN), distinguishing it from NKp44 and NKp46 which do bind these viral proteins. Binding assays with NKp30 fusion proteins, NK cell cytotoxicity assays against virus-infected cells European journal of immunology High 11536166
2003 TGFβ1 down-regulates NKp30 surface expression at the transcriptional level, leading to impaired NK-mediated killing of dendritic cells. NKp46 expression is not similarly affected. Flow cytometry for surface expression, transcriptional regulation analysis, NK cytotoxicity assays against DCs and tumor lines Proceedings of the National Academy of Sciences of the United States of America High 12646700
2004 Membrane-associated heparan sulfate proteoglycans (HSPGs), particularly glypican-1, are recognized by NKp30 on target cells; 6-O-sulfation and N-acetylation state of the glucose building unit affect this recognition and NK cell lysis. NK cytotoxicity assays with CHO cells lacking HS, heparanase treatment, glypican-1 siRNA knockdown, competitive inhibition experiments Journal of immunology Medium 15294952
2005 NKp30-mediated NK cell lysis of autologous APCs and DCs is dependent on phosphatidylinositol 3-kinase (PI-3K) signaling; PI-3K inhibitors LY294002 and wortmannin reduce NKp30-triggered killing and Akt/PKB activation. PI-3K inhibitor treatment (LY294002, wortmannin), redirected killing assays, Akt/PKB phosphorylation analysis European journal of immunology High 11385609
2005 NKp30 engagement induces NK cell secretion of TNFα and IFNγ, which in turn promotes DC maturation. This function is controlled by HLA-specific inhibitory NK receptors (KIR/NKG2A). Perforin-deficient NK cells can still induce cytokine-dependent DC maturation via NKp30, dissecting cytotoxic from cytokine-secretory NKp30 functions. NKp30-blocking mAb, NK-DC co-culture, cytokine neutralization (anti-TNFα), NK cell supernatant transfer, perforin-deficient NK cell analysis Blood High 15784725
2005 Human cytomegalovirus pp65 (the main tegument protein) directly and specifically interacts with NKp30, causing dissociation of the associated CD3ζ chain from NKp30 and consequently reducing NK cell cytotoxicity. Direct binding assays, co-immunoprecipitation, functional NK cytotoxicity assays, CD3ζ dissociation analysis Nature immunology High 15821739
2007 The nuclear protein BAT3 (BAG-6/HLA-B-associated transcript 3) is released from tumor cells, binds directly to NKp30, and triggers NKp30-mediated NK cytotoxicity. BAT3 is necessary for tumor rejection in a multiple myeloma model. Co-immunoprecipitation with NKp30, direct binding assays, tumor rejection model (in vivo), NKp30-blocking assays Immunity High 18055229
2009 B7-H6, a novel member of the B7 family, is a tumor cell surface ligand for NKp30 that triggers NKp30-mediated NK cell cytotoxicity and cytokine secretion. B7-H6 is not detected in normal human tissues but is expressed on tumor cells. Protein identification by mass spectrometry, direct binding assays, NKp30-Fc fusion protein pulldown, NK cell activation assays, flow cytometry of normal vs. tumor tissues The Journal of experimental medicine High 19528259
2009 MDSCs from hepatocellular carcinoma patients inhibit NK cell cytotoxicity and cytokine secretion via NKp30 in a cell-contact-dependent but arginase-independent manner. NK-MDSC co-culture, NKp30-blocking antibody experiments, cytotoxicity assays, cytokine measurement Hepatology Medium 19551844
2009 NKp30, NKp44, and NKp46 bind to different heparan sulfate/heparin sequences. NKp30 and NKp44 have approximately one order of magnitude higher affinity for synthetic HS/heparin than NKp46. NKp30 and NKp44 prefer highly charged HS structures but with different modification patterns. Microarray binding experiments, surface plasmon resonance (SPR) with synthetic HS/heparin oligosaccharides Journal of proteome research Medium 19196184
2011 Crystal structure of NKp30 bound to its ligand B7-H6 was determined. NKp30, a CD28 family member, engages B7-H6 using both front and back β-sheets of its Ig-like domain (via the side and face of the β-sandwich), a mode distinct from CTLA-4 and PD-1 inhibitory complexes. B7-H6 contacts NKp30 through CDR-like loops of its V-like domain. X-ray crystallography of NKp30-B7-H6 complex The Journal of experimental medicine High 21422170
2011 Crystal structure of NKp30 extracellular domain revealed an I-type Ig-like fold structurally distinct from NKp44 and NKp46. Ligand binding involves the F strand and surrounding residues (C strand, CD loop). The N-terminal domain of B7-H6 is sufficient for NKp30 recognition. X-ray crystallography, peptide epitope mapping, solution binding studies, site-directed mutagenesis of NKp30, cytolytic killing assays Proceedings of the National Academy of Sciences of the United States of America High 21444796
2011 NKp30-mediated signaling activates the canonical NF-κB pathway in NK cells, leading to IκB degradation and nuclear translocation of p65/p50 NF-κB heterodimer. This activation is blocked by the Syk inhibitor piceatannol. IκB degradation assays, EMSA, fluorescence microscopy, NF-κB reporter assay, Syk inhibitor treatment, NK-target cell conjugation assays Journal of immunology High 18025182
2011 Poxviral hemagglutinin (VV and ECTV) acts as a novel ligand for NKp30 on infected cells, but unlike NKp46 activation, VV HA blocks NKp30-triggered NK activation, representing an immune escape mechanism at late stages of infection. NCR-CD3ζ reporter cell assays, selectively silenced NCR expression (siRNA), recombinant soluble HA binding, NK cytotoxicity assays PLoS pathogens High 21901096
2012 NKp30 is required for NK cell-fungal conjugate formation, PI3K signaling, and perforin release to mediate recognition and killing of fungal pathogens Cryptococcus and Candida. Unbiased receptor identification, NKp30-blocking antibodies, PI3K signaling assays, perforin release assays, conjugate formation assays Cell host & microbe High 24139398
2012 NKp30 accumulates at the immune synapse interface between NK92 cells and HeLa tumor cells together with LFA-1. NKp30 blockade inhibits degranulation, cytotoxicity, and cytokine secretion but does not prevent NK-target cell conjugation. NKp30 ligation activates the Erk1/2 signaling pathway. Confocal microscopy of NK immunological synapse, NKp30 blocking antibody, Erk1/2 phosphorylation analysis, degranulation assays Immunological investigations Medium 22221078
2012 NKp30 is required for oHSV-triggered NK cell killing of glioblastoma cells; oHSV infection upregulates NKp30 and NKp46 ligands on glioblastoma cells. Ncr1-/- mice show increased HSV titers and improved oHSV efficacy. NKp30/NKp46 blocking antibodies, Ncr1-/- mouse model, NK adoptive transfer, in vitro killing assays Nature medicine High 23178246
2012 NKp30 engagement on Vδ1 T cells triggers production of CCL3/MIP-1α, CCL4/MIP-1β, and CCL5/RANTES (but not CXCL12), and this chemokine secretion suppresses CCR5-tropic HIV-1 replication in CD4+/CCR5+ cells. NKp30 blocking and cross-linking assays on Vδ1 T cells, chemokine measurement, HIV-1 replication assays in CD4+ PM1 cells Blood Medium 22403253
2013 BAG-6 C-terminal fragment (residues 686-936) forms a noncovalent dimer and is sufficient for high-affinity binding to NKp30 (KD < 100 nM). This fragment inhibits NKp30-dependent signaling, IFN-γ release, and NK cell degranulation in the presence of tumor target cells. Domain mapping, recombinant protein production, biophysical binding assays, NK cell functional assays (IFN-γ, degranulation) The Journal of biological chemistry High 24133212
2013 B7-H6 expression is induced on proinflammatory CD14+CD16+ monocytes and neutrophils by TLR ligands or proinflammatory cytokines (IL-1β, TNFα), extending its role beyond tumor immunosurveillance to inflammatory/infectious conditions. Flow cytometry, in vitro stimulation assays, in vivo patient sample analysis Blood Medium 23687088
2013 HDAC inhibitors (pan- or class I, particularly HDAC2/3) downregulate B7-H6 surface expression by reducing histone acetylation at the B7-H6 promoter, leading to decreased NKp30-dependent NK cell effector functions. HDAC inhibitor treatment, siRNA knockdown of HDAC2/3, luciferase reporter assay, chromatin immunoprecipitation (ChIP), NK cell functional assays Blood High 23801635
2014 Tumor cell shedding of B7-H6 is mediated by cell surface metalloproteinases ADAM-10 and ADAM-17. Inhibiting this shedding increases surface B7-H6 and enhances NKp30-mediated NK cell activation. Pharmacological ADAM inhibitors, siRNA knockdown of ADAM-10 and ADAM-17, flow cytometry for surface B7-H6, NK cell activation assays Cancer research High 24780758
2014 Tumor-released soluble Galectin-3 directly binds to NKp30 (confirmed by SPR) and inhibits NKp30-mediated but not NKG2D-mediated NK cytolysis. Genetic knockdown of Galectin-3 increases tumor sensitivity to NK killing in vitro and in xenograft models. NKp30-Fc immunoprecipitation, surface plasmon resonance, NK-tumor co-culture assays, shRNA knockdown, xenograft model with NK adoptive transfer The Journal of biological chemistry High 25315772
2007 NKp30 glycosylation state affects its binding to heparan sulfate; N-linked glycans on NKp30 can occlude the HS binding site. Removal of N-linked glycans restores heparan sulfate-dependent binding to tumor cells. Soluble heparan sulfate enhances IFNγ secretion by NKp30-activated NK cells. Enzymatic deglycosylation, binding assays with multiple recombinant NKp30 forms, SPR, NK cell IFNγ assay Glycobiology Medium 18006589
2012 The stalk region of NKp30 (flexible region between ectodomain and transmembrane domain) is an important but previously unrecognized module for ligand recognition and signaling. Glycosylation at three N-linked sites differentially affects ligand binding affinity and signaling; the degree of glycosylation provides a switch modulating NKp30 ligand binding properties. NKp30-Fc fusion protein panel, mutational analysis of glycosylation sites, cellular binding assays, functional signaling assays The Journal of biological chemistry High 22807449
2007 NKp30-mediated NK killing of filovirus-infected dendritic cells is dependent on NKp30 upregulation; gene expression knockdown directly linked NK lysis of infected DCs to NKp30 activation. Killing proceeds via perforin and CD95L mechanisms. Gene expression knockdown (siRNA), cytotoxicity assays, perforin/CD95L blocking Cellular microbiology Medium 17381429
2008 In uterine decidual NK cells, NKp30 engagement (but not NKp46) triggers production of IFNγ, TNFα, MIP-1α, MIP-1β, and GM-CSF, while NKp46 (but not NKp30) engagement triggers cytotoxicity (calcium mobilization, perforin polarization, granule exocytosis). This demonstrates a differential role for NKp30 vs. NKp46 in cytokine vs. cytotoxic functions in decidual NK cells. Multicolor flow cytometry, mAb-specific receptor engagement, calcium mobilization assay, perforin polarization assay, granule exocytosis assay Journal of immunology High 18713971
2007 NKp30 directly mediates NK cell recognition of P. falciparum-parasitized erythrocytes via interaction with the DBL-1α domain of PfEMP-1. This interaction leads to perforin production and granzyme B release. Pre-treatment of NK cells with DBL-1α peptides abolishes both interaction and killing. NKp30-Ig fusion protein binding assays, competitive peptide inhibition, perforin/granzyme B release assays The Journal of infectious diseases Medium 17436233
2007 NKp30-mediated killing in NK cells requires RAB27A function, as NK killing via NKp30 (but not CD16) is impaired in Griscelli syndrome patients with RAB27A mutations. CD16 triggers Vav1 phosphorylation whereas NKp30 does not, demonstrating distinct downstream signaling pathways. Patient NK cells from Griscelli syndrome (RAB27A mutation), redirected killing assays, phosphorylation analysis of Vav1 Blood High 17255357
2015 NKp30 is expressed on a subset of human ILC2s and upon interaction with its cognate ligand B7-H6 induces rapid production of type 2 cytokines. This activation can be blocked by NKp30-blocking antibody or the inhibitory ligand galectin-3. Flow cytometry, NKp30-B7-H6 co-culture, NKp30-blocking antibody, galectin-3 inhibition, cytokine measurement Journal of immunology Medium 26582946
2016 The proto-oncogene Myc (c-Myc and N-Myc) drives B7-H6 expression by binding a functional site in the B7-H6 promoter. Inhibition or knockdown of c-Myc/N-Myc decreases B7-H6 expression and impairs NKp30-mediated NK cell degranulation. Luciferase reporter assays, chromatin immunoprecipitation (ChIP), c-Myc/N-Myc siRNA/shRNA, pharmacological c-Myc inhibition, NK degranulation assay Oncoimmunology High 27622013
2017 NKp30-B7H6 interaction activates ILC2s to secrete IL-13, which in turn activates monocytic MDSCs in acute promyelocytic leukemia, forming an immunosuppressive axis. Disrupting this axis by blocking PGD2, IL-13, or NKp30 restores immune cell levels and improves survival. Patient sample analysis, blocking antibodies against PGD2, NKp30, IL-13, in vivo survival analysis, flow cytometry Nature communications Medium 28928446
2020 NKp30 forms oligomers dependent on its N-glycosylation. NKp30 expressed with simple N-glycans forms oligomers, but enzymatic deglycosylation reduces NKp30 to monomers. Crystal structure of glycosylated NKp30-B7-H6 complex revealed a glycosylation-induced mode of NKp30 dimerization. The stalk region and glycosylation affect ligand affinity. X-ray crystallography, enzymatic deglycosylation, size exclusion chromatography, binding affinity assays Cancers High 32708305
2018 NK cells lyse Th2-polarizing DCs via NKp30 and DNAM-1. NK cell MTOC polarization and LFA-1 accumulation at the immune synapse occurs with immature and Th2-polarizing DCs (but not Th1-polarizing DCs), indicating assembly of an activating NK synapse. Antibody blockade of NKp30 or DNAM-1 abrogates lysis. Confocal microscopy, time-lapse live-cell microscopy, antibody blocking of NKp30 and DNAM-1, degranulation assays Journal of immunology Medium 30120122
2019 In hepatocellular carcinoma, NKp30-positive NK cells have reduced expression of immunostimulatory NCR3 splice variants and increased expression of inhibitory variants. Exposure of NK cells to B7-H6-expressing HCC cells down-modulates NKp30, an effect prevented by siRNA-mediated B7-H6 knockdown, suggesting chronic ligand engagement drives inhibitory NKp30 isoform expression. Flow cytometry, RT-PCR splice variant analysis, NK-HCC cell co-culture, siRNA knockdown of B7-H6, tumor-infiltrating lymphocyte analysis Hepatology Medium 30153337
2018 IL-15 can de novo induce NKp30 expression in a population of CD8+ T cells. The adaptor FcεRIγ is concomitantly induced and is required for NKp30 cell-surface expression and function in these CD8+ T cells. FcεRIγ expression requires promoter demethylation, and is accompanied by acquisition of Syk and PLZF. Flow cytometry, in vitro IL-15 stimulation, FcεRIγ knockdown/overexpression, promoter methylation analysis, xenograft tumor model Proceedings of the National Academy of Sciences of the United States of America High 29895693
2024 IL-2 is specifically required for NKp30 (but not NKp46) surface expression and NKp30-dependent NK cell cytotoxicity against myeloid leukemia cells. IL-2 deprivation selectively downregulates NKp30 despite shared adaptor requirements with NKp46. Ectopic overexpression of immunostimulatory NKp30 isoforms (NKp30a or NKp30b) rescues NK cell cytotoxicity against B7-H6-expressing tumor cells in vivo without IL-2. IL-2 deprivation assays, NKp30 isoform overexpression, NK92/NK92MI cell comparison, in vivo xenograft model Frontiers in immunology Medium 38698855

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells. The Journal of experimental medicine 739 11828009
1999 Identification and molecular characterization of NKp30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells. The Journal of experimental medicine 599 10562324
2003 Transforming growth factor beta 1 inhibits expression of NKp30 and NKG2D receptors: consequences for the NK-mediated killing of dendritic cells. Proceedings of the National Academy of Sciences of the United States of America 581 12646700
2009 The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans. The Journal of experimental medicine 544 19528259
2009 Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor. Hepatology (Baltimore, Md.) 536 19551844
2001 Recognition of viral hemagglutinins by NKp44 but not by NKp30. European journal of immunology 308 11536166
2005 NK-dependent DC maturation is mediated by TNFalpha and IFNgamma released upon engagement of the NKp30 triggering receptor. Blood 302 15784725
2005 Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus. Nature immunology 283 15821739
2007 Human leukocyte antigen-B-associated transcript 3 is released from tumor cells and engages the NKp30 receptor on natural killer cells. Immunity 270 18055229
2003 The impaired NK cell cytolytic function in viremic HIV-1 infection is associated with a reduced surface expression of natural cytotoxicity receptors (NKp46, NKp30 and NKp44). European journal of immunology 250 12938217
2017 Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis. Nature communications 202 28928446
2011 Differentiation of human peripheral blood Vδ1+ T cells expressing the natural cytotoxicity receptor NKp30 for recognition of lymphoid leukemia cells. Blood 187 21633088
2014 Metalloprotease-mediated tumor cell shedding of B7-H6, the ligand of the natural killer cell-activating receptor NKp30. Cancer research 171 24780758
2012 NK cells impede glioblastoma virotherapy through NKp30 and NKp46 natural cytotoxicity receptors. Nature medicine 168 23178246
2009 Low NKp30, NKp46 and NKG2D expression and reduced cytotoxic activity on NK cells in cervical cancer and precursor lesions. BMC cancer 168 19531227
2015 B7-H6-mediated downregulation of NKp30 in NK cells contributes to ovarian carcinoma immune escape. Oncoimmunology 151 26137398
2009 Natural cytotoxicity receptors NKp30, NKp44 and NKp46 bind to different heparan sulfate/heparin sequences. Journal of proteome research 130 19196184
2015 Clinical impact of the NKp30/B7-H6 axis in high-risk neuroblastoma patients. Science translational medicine 123 25877893
2005 Interaction between human NK cells and bone marrow stromal cells induces NK cell triggering: role of NKp30 and NKG2D receptors. Journal of immunology (Baltimore, Md. : 1950) 122 16272287
2013 Induction of B7-H6, a ligand for the natural killer cell-activating receptor NKp30, in inflammatory conditions. Blood 119 23687088
2012 An NKp30-based chimeric antigen receptor promotes T cell effector functions and antitumor efficacy in vivo. Journal of immunology (Baltimore, Md. : 1950) 114 22851709
2004 Membrane-associated heparan sulfate proteoglycans are involved in the recognition of cellular targets by NKp30 and NKp46. Journal of immunology (Baltimore, Md. : 1950) 114 15294952
2013 Downregulation of the activating NKp30 ligand B7-H6 by HDAC inhibitors impairs tumor cell recognition by NK cells. Blood 113 23801635
2014 Tumor-released Galectin-3, a soluble inhibitory ligand of human NKp30, plays an important role in tumor escape from NK cell attack. The Journal of biological chemistry 111 25315772
2008 Critical and differential roles of NKp46- and NKp30-activating receptors expressed by uterine NK cells in early pregnancy. Journal of immunology (Baltimore, Md. : 1950) 111 18713971
2001 NK cell-mediated lysis of autologous antigen-presenting cells is triggered by the engagement of the phosphatidylinositol 3-kinase upon ligation of the natural cytotoxicity receptors NKp30 and NKp46. European journal of immunology 110 11385609
2010 Reduced frequencies of NKp30+NKp46+, CD161+, and NKG2D+ NK cells in acute HCV infection may predict viral clearance. Journal of hepatology 103 21168454
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2013 The NK receptor NKp30 mediates direct fungal recognition and killing and is diminished in NK cells from HIV-infected patients. Cell host & microbe 94 24139398
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2007 Expression analysis of the ligands for the Natural Killer cell receptors NKp30 and NKp44. PloS one 79 18092004
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2007 A Duffy binding-like domain is involved in the NKp30-mediated recognition of Plasmodium falciparum-parasitized erythrocytes by natural killer cells. The Journal of infectious diseases 70 17436233
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2001 Identification, molecular cloning and functional characterization of NKp46 and NKp30 natural cytotoxicity receptors in Macaca fascicularis NK cells. European journal of immunology 58 11745374
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2016 NKp30 isoforms and NKp30 ligands are predictive biomarkers of response to imatinib mesylate in metastatic GIST patients. Oncoimmunology 46 28197361
2013 Hepatitis C virus-infected cells downregulate NKp30 and inhibit ex vivo NK cell functions. Journal of immunology (Baltimore, Md. : 1950) 45 23960237
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2015 Expression of NKp30, NKp46 and DNAM-1 activating receptors on resting and IL-2 activated NK cells from healthy donors according to CMV-serostatus and age. Biogerontology 41 25991472
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2007 NKp30-dependent cytolysis of filovirus-infected human dendritic cells. Cellular microbiology 39 17381429
2008 Umbilical cord blood T cells express multiple natural cytotoxicity receptors after IL-15 stimulation, but only NKp30 is functional. Journal of immunology (Baltimore, Md. : 1950) 38 18802053
2012 The stalk domain and the glycosylation status of the activating natural killer cell receptor NKp30 are important for ligand binding. The Journal of biological chemistry 37 22807449
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2013 A soluble fragment of the tumor antigen BCL2-associated athanogene 6 (BAG-6) is essential and sufficient for inhibition of NKp30 receptor-dependent cytotoxicity of natural killer cells. The Journal of biological chemistry 34 24133212
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2015 HER2-specific immunoligands engaging NKp30 or NKp80 trigger NK-cell-mediated lysis of tumor cells and enhance antibody-dependent cell-mediated cytotoxicity. Oncotarget 33 26392331
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2007 NKp30 ligation induces rapid activation of the canonical NF-kappaB pathway in NK cells. Journal of immunology (Baltimore, Md. : 1950) 29 18025182
2015 Enhancing natural killer cell-mediated lysis of lymphoma cells by combining therapeutic antibodies with CD20-specific immunoligands engaging NKG2D or NKp30. Oncoimmunology 28 26942070
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2016 NKp30 isoforms and NKp46 transcripts in metastatic melanoma patients: Unique NKp30 pattern in rare melanoma patients with favorable evolution. Oncoimmunology 23 28123867
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2017 Natural Killer Cells from the Subcutaneous Adipose Tissue Underexpress the NKp30 and NKp44 in Obese Persons and Are Less Active against Major Histocompatibility Complex Class I Non-Expressing Neoplastic Cells. Frontiers in immunology 20 29163547
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2015 First Trimester Pregnancy Loss and the Expression of Alternatively Spliced NKp30 Isoforms in Maternal Blood and Placental Tissue. Frontiers in immunology 18 26082773
2013 Analysis of NKp30/NCR3 isoforms in untreated HIV-1-infected patients from the ANRS SEROCO cohort. Oncoimmunology 18 23802087
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