NCR1 Antibody

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Description

Definition and Target Profile of NCR1 Antibody

NCR1 antibodies target the NCR1 protein (NKp46/CD335), a 46 kDa type I transmembrane glycoprotein belonging to the immunoglobulin superfamily . This receptor is a pan-NK cell marker, expressed on all human NK cells regardless of activation state, and plays a pivotal role in initiating cytotoxicity, calcium mobilization, and cytokine production .

Research Applications of NCR1 Antibodies

NCR1 antibodies are employed across immunology, oncology, and autoimmune disease research:

Table 1: Key Applications and Findings

ApplicationStudy ModelKey FindingsSources
Multiple Sclerosis (MS)Human CNS tissueNCR1 mRNA elevated in active MS lesions; astrocytes, not NK cells, express NCR1
Type 1 Diabetes (T1D)NOD miceAnti-NCR1 (NCR1.15) reduced diabetes incidence by blocking NKp46-mediated β-cell lysis
Cancer ImmunotherapyTumor cell linesNCR1 antibodies inhibit NK-mediated tumor lysis by blocking receptor-ligand interactions
Viral Infection StudiesInfluenza modelsNCR1 binds viral haemagglutinin, enhancing NK cell recognition of infected cells

Mechanistic Insights from Recent Studies

  • Autoimmunity: In MS, NCR1+ astrocytes outnumber NK cells in lesions, suggesting astrocyte-mediated innate immune signaling contributes to neuroinflammation .

  • Therapeutic Blockade: The monoclonal antibody NCR1.15 (anti-mouse NKp46) suppressed degranulation and cytotoxicity in vitro and reduced diabetes incidence in vivo by 60% .

  • Cross-Reactivity: Commercial antibodies like AF1850 detect human NCR1 in ELISA/Western blot with <5% cross-reactivity to mouse NKp46, enabling species-specific studies .

Technical Considerations

  • Antibody Validation: Clone specificity is critical. For example:

    • NCR1.15: Targets mouse NKp46 (K<sub>d</sub> = 10.6 nM), no cross-reactivity with human NKp46 .

    • 29A1.4: Validated for flow cytometry in murine models .

    • AF1850: Used in IHC/ELISA for human NCR1, localized to lymphocyte cytoplasm .

  • Limitations: Low NCR1 density on NK cells in some individuals (“NCR dull” phenotype) may reduce antibody efficacy in functional assays .

Future Directions

  • Ligand Discovery: Only influenza haemagglutinin is confirmed; unidentified ligands in autoimmune contexts require characterization .

  • Astrocyte Targeting: NCR1+ astrocytes in MS lesions could be modulated to attenuate neuroinflammation .

  • Clinical Translation: Antibodies like NCR1.15 may delay T1D onset if applied during early insulitis .

Product Specs

Buffer
Liquid in PBS containing 50% glycerol, 0.5% BSA and 0.02% sodium azide.
Form
Liquid
Lead Time
We typically dispatch products within 1-3 business days of receiving your order. Delivery times may vary depending on the purchasing method and location. Please consult your local distributor for specific delivery timelines.
Synonyms
NCR1; LY94; Natural cytotoxicity triggering receptor 1; Lymphocyte antigen 94 homolog; NK cell-activating receptor; Natural killer cell p46-related protein; NK-p46; NKp46; hNKp46; CD antigen CD335
Target Names
Uniprot No.

Target Background

Function
NCR1 (Natural Cytotoxicity Receptor 1), also known as NKp46, is a cytotoxicity-activating receptor that plays a significant role in the enhanced efficiency of activated natural killer (NK) cells to mediate tumor cell lysis.
Gene References Into Functions
  1. Research has shown that decreased expression of the activating receptor NKp46 on peripheral blood NK cells is positively associated with gastric cancer progression. PMID: 30255106
  2. HIF-1alpha inhibits the NCR1/NKp46 pathway through up-regulation of miR-224, which affects the killing capability of NK cells on prostate cancer, leading to immune escape of tumor cells. PMID: 29885835
  3. Studies have demonstrated that mutant NKp46 W32R exhibits aberrant glycosylation, accumulates in the endoplasmic reticulum, and demonstrates instability on the cell surface. PMID: 28134248
  4. Low NKp46 expression on NK cells has been linked to Nasopharyngeal Carcinoma. PMID: 29580037
  5. Signaling through the natural killer cell receptor NKp46 (human) and Ncr1 (mouse) has been observed to induce interferon-gamma (IFN-gamma) secretion from intratumoral natural killer cells. PMID: 29329948
  6. Findings indicate that HIV reservoir size is dependent on the presence of a defined NK cell population characterized by a specific transcriptional signature: high NCR (NKp46 and NKp30) and IFN-gamma inducibility upon NCR and cytokine receptor engagement. PMID: 28956765
  7. Cleavage of NKp46 by Cathepsin G significantly impairs NKp46-mediated responses of Natural killer cells. PMID: 27587403
  8. The interaction between NKp46 and its ligand contributes to NK cell activation. PMID: 28328926
  9. Research has shown that the NKp46-activating receptor recognizes an unknown ligand expressed by human metapneumovirus-infected cells. PMID: 28191644
  10. Intrahepatic NKp46 NK cells have been shown to exhibit anti-HCV activity via cell-to-cell contact. The variation in the NKp46 proportion among individuals may explain the diversity of HCV resistance observed. PMID: 26714120
  11. Results indicate that endogenous levels of IFN-alpha secreted by plasmacytoid dendritic cells induce natural killer cells to lyse HIV-1-infected autologous CD4+ primary T cells via the engagement of NKp46 and NKG2D. PMID: 26372382
  12. NKp46 has been implicated in the production of serine proteases and interleukin-22 in human mast cells. PMID: 25940096
  13. Age and CMV serostatus have been found to influence the expression of NKp30, NKp46, and DNAM-1 activating receptors on resting and IL-2 activated natural killer cells. PMID: 25991472
  14. Ncr1-Noe proteins accumulate in the endoplasmic reticulum, and the expression of Ncr1-Noe proteins, but not WT Ncr1, leads to increased Helios expression. PMID: 26371250
  15. Data suggest that regulatory dendritic cells (regDC) restrain IFN-gamma secretion by NK cells through secretion of interleukin-10 (IL-10), engagement of MHC class I-specific inhibitory receptors, and the activating receptor NKp46. PMID: 26232426
  16. Expression of NKp46/NCR1 in NK cells was significantly higher in untreated severe aplastic anemia patients compared to those in remission SAA and controls. This may explain the hyperfunction of the immune system in SAA patients. PMID: 26554241
  17. Downregulated NKG2D, NKp46, and DNAM-1 receptors associated with impaired NK cell effector function are significant biomarkers of advanced disease with a poor prognosis in melanoma patients. PMID: 24769842
  18. Women, both with and without endometriosis, with larger populations of cytotoxic CD16(+) uterine NK cells and/or higher populations of NKp46(+)CD56(+) cells may be at greater risk of infertility due to an inflammatory environment during implantation or later stages. PMID: 24807109
  19. IL-15+IL-12 has an immunomodulatory effect on NK cell subsets from HIV-infected individuals, characterized by down-regulation of iNKRs, elevation of activatory receptors NKp46 and NKG2D, and induction of coreceptor NKp80. PMID: 22715368
  20. NKp46 identifies pathologically activated natural killer cells, which may result from a loss of homeostatic control of activating receptor expression in hepatitis C virus infection. PMID: 23665989
  21. NKp46 is expressed on CD4 lymphocytes in mycosis fungoides and Sezary syndrome. PMID: 23900021
  22. Cytokine stimulation combined with natural killer cell receptor engagement are necessary for the functional diversity of human natural killer cells. PMID: 23490421
  23. NKp46 is involved in cytokine production of CD56+ NK cells in the uterine endometrium. PMID: 23311919
  24. PLS3, Twist, KIR3DL2, and NKp46 gene expression can serve as a model for efficient molecular Sezary syndrome diagnosis. PMID: 23429988
  25. NKp46 expression in hepatitis C virus replication controls the modulation of liver fibrosis. PMID: 22532190
  26. Race and gender-related variation has been found in NKp46 receptor expression, leading to differential anti-hepatitis C virus immunity. PMID: 22505144
  27. NKp46 is expressed in all investigated cases of transformed mycosis fungoides. PMID: 22621189
  28. Studies suggest that NKp46 dimerization contributes to NKp46-mediated lysis by NK cells. PMID: 22615207
  29. NKp46 levels remain stable on natural killer cells that persist at one week post-liver transplant in pediatric patients. PMID: 22360401
  30. NKp46 plays an important role in the inhibition of liver fibrosis. PMID: 22198715
  31. Research has demonstrated the expression of NCR1 on astrocytes in MS tissue. PMID: 22212381
  32. RUNX3 (runt-related transcription factor 3) plays a role in the transcriptional regulation of natural cytotoxicity receptor 1 (NCR1/NKp46), an activating natural killer (NK) cell receptor. PMID: 22253448
  33. Findings show that NK cells can significantly accelerate neutrophil apoptosis, a process that is dependent on cell-cell contact and mediated by the activating NK cell receptor NKp46 and the Fas pathway. PMID: 22231698
  34. Decreased NKp46 expression is associated with altered NK-cell function in pediatric transplant patients with PTLD. PMID: 22105417
  35. Studies investigate whether NKp46 is involved in the killing of human beta cells. PMID: 21849674
  36. NKp46 identifies a functionally distinct NKT subset that appears to be directly susceptible to leukemic transformation when IL-15 is overexpressed. PMID: 21364281
  37. Data show that an increase in 2B4-expressing NK cells and a decrease in NKp46(+) NK cells occurred following intramuscular influenza vaccination. PMID: 21214542
  38. Peripheral blood malignant CD4(+) T lymphocytes from patients with Sezary syndrome, an aggressive form of cutaneous T-cell lymphoma, express NKp46 at their cell surface. PMID: 21191411
  39. NKp46 interacts with heparin and heparan sulfate, highly sulfated glycans, and multimeric alpha2,3-NeuAc-containing N-glycan; these glycans interact primarily with basic amino acids in NKp46. PMID: 21329668
  40. Data indicate that only NKp46 appeared to be involved in the NK response. PMID: 21030563
  41. NKp46 is essential for the development of type 1 diabetes. PMID: 20023661
  42. The NKp46 receptor participates in NK cell-mediated lysis of cells infected with the intracellular pathogen Mycobacterium tuberculosis, an activity that is reduced in tuberculosis patients compared to healthy donors. PMID: 11907104
  43. The crystal structure of the human natural killer (NK) cell activating receptor NKp46 has been determined. PMID: 12960161
  44. NKp46 interacts with both viral hemagglutinins and the unknown tumor ligands through distinct mechanisms. PMID: 14504081
  45. CD59 is physically associated with NKp46 and NKp30, and it activates human NK cell-mediated cytotoxicity. PMID: 14635045
  46. Natural cytotoxicity receptor (NCR) and NK receptor member D of the lectin-like receptor family (NKG2D) were identified as the key NK activating receptors for bone marrow-derived myeloma cell recognition. PMID: 15328155
  47. NKp46 is not only a triggering molecule essential for antitumor activity but is also a surface receptor involved in natural killer cell suicide. PMID: 15728472
  48. Research has examined residues in NKp46 that may be involved in heparan sulfate binding on tumor cells. PMID: 16262248
  49. A defect in cytotoxic effector function has been associated with a reduced surface expression of activating NK receptors (NKp30, NKp46, and NKG2D) on CD56(dim) NK cells compared to uninfected newborns. PMID: 16690951
  50. The natural cytotoxicity receptor NKp46 was found to be required for the killing of all myeloma cell lines analyzed. PMID: 17875681

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Database Links

HGNC: 6731

OMIM: 604530

KEGG: hsa:9437

STRING: 9606.ENSP00000291890

UniGene: Hs.97084

Protein Families
Natural cytotoxicity receptor (NCR) family
Subcellular Location
Cell membrane; Single-pass type I membrane protein.
Tissue Specificity
Selectively expressed by both resting and activated NK cells.

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Applications : Flow Cytometric Analysis

Sample type: NK cell

Review: Multiple labeling of surface receptors was performed on goat NK cells against the molecules: CD16, CD14, NKp46, CD3, and SLAM. Representative FACS plots showing freshly sorted goat CD16+CD14− cell labeled with anti-NKp46 mAb, anti-CD3 mAb, or isotype control mAb.

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