Natural killer (NK) cells are an important part of the innate immune system and have dual functions of cytotoxicity and immune modulation. The immune activity of NK cells is mediated by a large number of cell surface receptors that recognize different ligands and mediate different signaling pathways.
Of the four known natural cytotoxic receptors (NCRs), three are constitutively expressed in NK cells (NKP30, NKP46, and NKP80), while NKP44 is only present on the surface of activated NK cells. The binding of these receptors to their ligands is delivered to the cellStronglyactivation signal. Signal transduction of NCRs is performed by the related protein DAP12, the ITAM motif in NKP44, FC RI in NKP30 and NKP46, and CD3δ (Figure 1). 
nkp30
NKP30 has a mass of 30 kDa and contains a 138-amino acid long Ig-like extracellular domain, a 19-amino acid transmembrane (TM) domain, and a 33-amino acid cytoplasmic tail. The extracellular domain of NKP30 contains an Ig-like fold that is connected to the transmembrane helix (red) by a short-stemmed domain. The Ig-like domain consists of eight chains forming two counterparallel lamellae (yellow) connected by a disulfide bond between Cys39 and Cys108 (Figure 2). The extracellular domain contains two potential sites for n-linked glycosylation involved in ligand binding.
The TM domain contains positively charged arginine residues that bind to negatively charged aspartic acid in the TM domain of the ITAM linker molecules CD3 and FC RI. This is also a common feature of other NK cell activation receptors. 
NKP30 is expressed on almost all human NK cells and is a type I transmembrane activating receptor of the immunoglobulin superfamily. NKP30-mediated responses are triggered by the binding of specific ligands, such as tumor cell-derived B7-H6, and trigger the secretion of cytotoxic mediators TNF-, IFN-, perforin, and granzyme.
A strong activation signal is transduced to cells when NKP30 binds to an agonist antibody or ligand, and signal transduction of this NCR occurs through the iTAM motif of FC RI and CD3 in NKP30 (Figure 3). NKP30 activation can induce cytotoxicity and cytokine secretion of NK cells, and plays an important role in anti-tumor, antiviral and anti-parasitic infections.
According to the market demand and research status, Jiman Biotech has launched NKP30 overexpression cell line, reporter gene detection cell line and related antibody products (see the end of the article for detailed data), which can be used for antibody screening, characterization and consistency evaluation, fully meet the needs of drug research and development, and help the clinical application of drugs.
NKP30 ligand
The NKP30 receptor may bind to a variety of ligand types. Poxvirus hemagglutinin (HA), which binds to NKP30 and acts as an antagonist;Human cytomegalovirus epithelial protein PP65 (HCMV PP65) is also able to block trigger signaling involving NKP30;Plasmodium falciparum erythrocyte membrane protein 1 (PFEMP-1) is identified as a strong activating ligand for NKP30 and NKP46 that, once bound, results in lysis of infected cells.
Tumor-associated NKP30 ligands
Ligand bat3
BAT3 (HLA-B-associated transcript 3, also known as BAG6, BCL2-associated Athanogene 6) is a protein chaperone that is overexpressed by tumor cells in response to stress signals. BAT3 promotes exosome-mediated metastasis in melanoma patients and has been identified as a prognostic biomarker for patients with hepatocellular carcinoma, gastrointestinal stromal tumor, and non-small cell lung cancer.
Ligand B7-H6The NKP30 ligand B7-H6 is little or poorly expressed in normal tissues and cells, and the expression of B7-H6 molecule is upregulated when cells become cancerous or infected. Unlike other B7 family proteins, B7-H6 is not expressed in normal human tissues under steady-state conditions, but is induced to be expressed in response to inflammatory stress. Correspondingly, B7-H6 has been shown to be expressed on a variety of different tumor tissues. B7-H6 binds to NKP30-activating receptors on natural killer cells and induces cytotoxicity, thereby promoting anti-tumor immune responses. In contrast, soluble B7-H6 (which can be produced by ADAM-mediated exodomain shedding) has also been shown to be associated with reduced NKP30 expression and natural killer cell dysfunction in some cancers, suggesting that B7-H6 may negatively modulate immune responses under certain conditions. In addition, B7-H6 has been found to promote tumor cell proliferation and inhibit apoptosis in studies using human breast cancer or glioma cell lines, further suggesting that B7-H6 may be involved in tumorigenesis. Similarly, high levels of B7-H6 expression in human ovarian cancer are positively correlated with tumor progression and metastasis.
Research pattern
At present, there are not many companies that have deployed NKP30, and most of them are in the preclinical development stage, mainly focusing on the research and development of antibody drugs. In addition, NKP30 has also been explored in chimeric antigen receptor T cells (CAR-T)*
Data display
The H NKp30 Reporter Jurkat Cell Line (Genomeditech GM-C29776) was activated using two NKP30 antibodies to validate the results.
The results were verified by the flow cytometry of the H NKP30 CHO-K1 cell line (Genomeditech GM-C29749) using Anti-NKP30 Higg1 Antibody (BGA-1833) (Genomeditech GM-49311AB).
The results were validated using the HNP30 HEK-293 cell line (Genomeditech GM-C30360) using anti-NKP30 Higg1 Antibody (BGA-1833) (Genomeditech GM-49311AB).
The results were validated by Cynomolgus NKP30 CHO-K1 cell line (Genomeditech GM-C33009) using anti-NKP30 Higg1 Antibody (BGA-1833) (Genomeditech GM-49311AB).
Jiman Biotech assists in drug research and development, closely follows the cutting-edge target information, and reserves hundreds of spot cells, covering nearly 200 targets in GPCR, cytokines, immune checkpoints, TAA and other fields. References:
1】doi: 10.1111/bph.15222