NCR3 Antibody
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Description
Definition and Biological Context
NCR3 (CD337/NKp30) is a type I transmembrane protein in the immunoglobulin superfamily, encoded in the MHC class III region. It facilitates NK cell cytotoxicity and cytokine secretion through interactions with ligands like B7-H6 and heparan sulfate glycosaminoglycans . NCR3 antibodies bind to this receptor, modulating its activity for therapeutic or experimental purposes.
Key Attributes
Mechanism of Action
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Activation: Cross-linking NCR3 with antibodies induces phosphorylation of the CD3ζ adaptor, triggering cytotoxic granule release and IFN-γ production .
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Immunosuppression: Certain isoforms (e.g., NKp30c) reduce CD3ζ association, skewing responses toward immunosuppressive cytokines like IL-10 .
Diagnostic and Experimental Uses
Therapeutic Development
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Bispecific Antibodies: Engineered constructs (e.g., CD20xNCR3.19) redirect NK cells to lyse B cell lymphomas or HER2+ breast cancers .
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Cytokine Secretion: High-affinity antibodies (e.g., NCR3.19) induce potent IFN-γ release compared to low-affinity clones (e.g., NCR3.12) .
Functional Screening Insights
A 2021 mammalian display screen identified NCR3-targeting antibodies with divergent efficacy :
| Antibody Clone | Cytotoxicity (Lysis %) | IFN-γ Secretion (pg/mL) |
|---|---|---|
| NCR3.19 | 85 ± 4 | 1,200 ± 90 |
| NCR3.12 | 45 ± 6 | 450 ± 60 |
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Efficacy Drivers: High-affinity binding and scFv domain orientation (LH > HL) optimize tumor targeting .
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Clinical Relevance: Gastrointestinal stromal tumor patients with NKp30c isoform exhibit poorer prognoses due to immunosuppressive NK responses .
Bispecific Antibody Performance
In a comparative study, NCR3-targeting bispecifics demonstrated efficacy rivaling anti-CD20 monoclonal antibodies :
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CD20xNCR3.19: Achieved 92% lysis of Daudi B cell lymphoma cells at 10 µg/mL.
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HER2xNCR3.19: Induced 78% lysis of SK-BR3 breast cancer cells.
Challenges
Product Specs
Buffer
Liquid in PBS containing 50% glycerol, 0.5% bovine serum albumin (BSA), and 0.02% sodium azide.
Form
Liquid
Lead Time
Typically, we can ship your orders within 1-3 business days of receipt. Delivery times may vary depending on the purchase method and location. Please consult your local distributors for specific delivery information.
Synonyms
NCR3; 1C7; LY117; Natural cytotoxicity triggering receptor 3; Activating natural killer receptor p30; Natural killer cell p30-related protein; NK-p30; NKp30; CD antigen CD337
Target Names
Uniprot No.
Target Background
Function
NCR3, also known as NKp30, is a cell membrane receptor found on natural killer (NK) cells. It plays a crucial role in activating NK cell cytotoxicity by binding to extracellular ligands such as BAG6 and NCR3LG1. This activation triggers NK cell-mediated destruction of neighboring cells expressing these ligands, contributing to the control of NK cell cytotoxicity against tumor cells, for example. The engagement of NCR3 by BAG6 also promotes the maturation of myeloid dendritic cells (DCs) through two mechanisms: eliminating DCs that haven't attained a mature phenotype and inducing the release of tumor necrosis factor alpha (TNFA) and interferon gamma (IFNG) from NK cells, which further enhances DC maturation.
Gene References Into Functions
- A study revealed that reduced expression of the activating receptor NKp30 on peripheral blood NK cells is positively correlated with the progression of gastric cancer. PMID: 30255106
- Low NKp30 expression on NK cells has been associated with nasopharyngeal carcinoma. PMID: 29580037
- Research suggests that NKp30 status can serve as a simple and early prognostic biomarker for identifying intermediate-risk patients with poor prognosis, who might otherwise be missed using existing risk stratification systems. PMID: 28548938
- Evidence indicates a sequence of events triggered by tumor-derived prostaglandin D2 (PGD2) that involves the natural cytotoxicity triggering receptor 3 (NKp30)-B7H6 antigen (B7H6) pathway. This pathway leads to significant activation and expansion of group 2 innate lymphoid cells (ILC2s). PMID: 28928446
- NKp44 and NKp30 splice variants profiles exhibit tissue/condition specificity and demonstrate similarities between placenta and cancerous tissues. PMID: 27765926
- Studies have found that carriers of the rs2736191-C NCR3 variant experience a significantly increased number of mild malaria episodes compared to non-carriers. This single nucleotide polymorphism (SNP) exhibits enhanced promoter activity in the NCR3 gene and involves a binding site for STAT4 and RUNX3. PMID: 29121672
- Findings indicate that HIV reservoir size is dependent on the presence of a specific NK cell population characterized by a distinctive transcriptional signature: high NCR (NKp46 and NKp30) and IFN-gamma inducibility upon NCR and cytokine receptor engagement. PMID: 28956765
- Data suggest that copy number variations of HLA-I and activation of the NKp30 pathway determine the sensitivity of gastric cancer cells to the cytotoxicity of natural killer cells. PMID: 26364607
- Research suggests that NK cells and NKp30 may play a role in the pathogenesis of antisynthetase syndrome. PMID: 27511738
- A study found that the stalk domains of NKp30 and NKp46, another NCR utilizing CD3zeta for signaling, were not interchangeable without significant impairments in folding, plasma membrane targeting, and/or ligand-induced receptor signaling. PMID: 27754869
- Age and cytomegalovirus (CMV) serostatus influence the expression of NKp30, NKp46, and DNAM-1 activating receptors on resting and IL-2-activated natural killer cells. PMID: 25991472
- The NKp30-B7-H6 interaction represents a novel cell contact mechanism mediating the activation of group 2 innate lymphoid cells. This discovery identifies a potential target for developing new therapeutics for atopic dermatitis and other atopic diseases. PMID: 26582946
- Research suggests that the NKP30-B7-H6 interaction might exacerbate hepatocyte damage, possibly through the upregulation of IL-32 expression in hepatitis B virus-related acute-on-chronic liver failure. PMID: 26241657
- The interaction between NKp30 and B7-H6 might contribute to the clinical outcomes of neuroblastoma patients. PMID: 25877893
- Research suggests a potential role for NKp30 isoforms in influencing liver damage and subsequent fibrosis during chronic hepatitis C infection. PMID: 26094914
- Studies have shown that in addition to NKG2D, human CEACAM1 can inhibit NK-cell activation through NKp30 or 2B4. PMID: 25824372
- The upregulation of DNAM-1 and NKp30, associated with improved NK cell activation, has been observed after long-term culture of mononuclear cells from patients with ovarian neoplasms. PMID: 24882570
- Tumor-released Galectin-3, a soluble inhibitory ligand of human NKp30, plays a significant role in tumor evasion of NK cell attacks. PMID: 25315772
- The allogeneic and xenogeneic anti-tumor effect of callithrix jacchus natural killer cells is dependent on the NKp30 and B7-H6 interaction. PMID: 25001651
- NKp30 is essential for natural killer cell-fungal conjugate formation, phosphatidylinositol 3-kinase (PI3K) signaling, and perforin release. PMID: 24139398
- Data suggest that the ectodomain of NKp30 forms functional homo-oligomers that mediate high-affinity binding to its corresponding cellular ligand B7-H6. PMID: 24275655
- Research has demonstrated that BAG-6(686-936) comprises a subdomain of BAG-6 that is sufficient for receptor docking and inhibition of NKp30-dependent NK cell cytotoxicity. This mechanism contributes to tumor immune escape. PMID: 24133212
- Findings suggest that NK cells may promote an NKp30-dependent inflammatory state in salivary glands. Blocking the B7H6/NKp30 axis could be clinically relevant in primary Sjogren's syndrome. PMID: 23884468
- Polymorphisms in HHIP, HDAC4, NCR3, and RARB may play a role in impaired lung function, beginning in early life. PMID: 23456936
- Research reveals that B7-H6 is not only involved in tumor immunosurveillance but also participates in the inflammatory response in infectious conditions. PMID: 23687088
- Cytokine stimulation combined with natural killer cell receptor engagement is required for the functional diversity of human natural killer cells. PMID: 23490421
- Data describe an immune escape mechanism of monoclonal gammopathy/multiple myeloma that occurs through downregulation of three major activating NK receptors (NCR3/NKp30, NKG2D, and CD244/2B4/p38) in bone marrow, which is undetectable in peripheral blood. PMID: 23360454
- Using a codon-optimized gene fragment, researchers reported remarkable yields for the extracellular domain of human NK cell receptor (NKp30ex) when produced on M9 minimal medium, even with low (2 g/L) glucose concentration. PMID: 23059620
- Natural cytotoxicity receptors play a major role in the recognition of cancer stem cells targets by NK cells. PMID: 23345327
- B7-H6:7D8 represents the first antibody-based molecule that stimulates NKp30-mediated NK cell cytotoxicity for therapeutic purposes. PMID: 23066150
- The stalk domain and glycosylation status of the activating natural killer cell receptor NKp30 are crucial for ligand binding. PMID: 22807449
- NKp30 chimeric antigen receptor-expressing T cells produce interferon (IFN)-gamma and kill B7-H6 ligand-expressing tumor cells in vivo. PMID: 22851709
- NKp30 expression is significantly increased on natural killer cells that persist at one week post-liver transplant in pediatric patients. PMID: 22360401
- NKp30 is a triggering receptor downstream of adhesion and plays a significant role in NK cell activation, degranulation, and cytotoxicity. PMID: 22221078
- A detailed analysis of clinical data showed a correlation between decreased NCR expression and poor prognosis factors, such as low hemoglobin levels, high (>30x10(9) per liter) lymphocyte counts, or elevated C-reactive protein. PMID: 22044312
- Alternatively spliced isoforms of NKp30 have been implicated in influencing the prognosis of gastrointestinal stromal tumors. PMID: 21552268
- Research provides insights into NKp30 ligand recognition and a framework for identifying potential unidentified ligands. PMID: 21444796
- The NKp30-B7-H6 structure revealed that this NK cell activating complex is distinct from the CTLA4-B7 and PD-1-PD-L T cell inhibitory complexes in both overall organization and detailed atomic interactions mediating binding and specificity. PMID: 21422170
- Observational study of gene-disease association. (HuGE Navigator) PMID: 20712903
- NKp30(high) cells are more effective in preventing hepatitis C infection in high-risk intravenous drug-addicted individuals. PMID: 20812318
- Observational study of gene-disease association. (HuGE Navigator) PMID: 19913121
- Observational study of gene-disease association. (HuGE Navigator) PMID: 20587610
- Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator) PMID: 20628086
- Observational study of gene-disease association. (HuGE Navigator) PMID: 20663564
- Selective cross-talk among natural cytotoxicity receptors (NKp46, NKp30, and NKp44) in human natural killer cells. PMID: 12731048
- CD59 is physically associated with NKp46 and NKp30 and activates human NK cell-mediated cytotoxicity. PMID: 14635045
- NKG2D, NKp30, NKp44, and NKp46 activation are affected by ligand-negative phenotype in bone marrow-derived progenitor cells, acquisition of cell-surface ligands during myeloid differentiation, and defective expression of ligands on malignant transformation. PMID: 15657183
- NKp30 is not only a triggering molecule essential for antitumor activity but is also a surface receptor involved in natural killer cell suicide. PMID: 15728472
- NK cell-mediated induction of dendritic cell maturation is dependent on NKp30. PMID: 15784725
- Heparan sulfate glycosaminoglycans are not ligands for NKp30, leaving open the question of the nature of the cellular ligand for this important NK cell activation receptor. PMID: 15972650
Database Links
Protein Families
Natural cytotoxicity receptor (NCR) family
Subcellular Location
Cell membrane; Single-pass type I membrane protein.
Tissue Specificity
Selectively expressed by all resting and activated NK cells and weakly expressed in spleen.
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