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- Table of Contents
Facts about C-type lectin domain family 9 member A.
.
Mouse | |
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Gene Name: | Clec9a |
Uniprot: | Q8BRU4 |
Entrez: | 232414 |
Belongs to: |
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No superfamily |
CD370; CLEC9a; C-type lectin domain family 9 member A; C-type lectin domain family 9, member A; DNGR1; HEEE9341; UNQ9341
Mass (kDA):
27.014 kDA
Mouse | |
---|---|
Location: | 6|6 F3 |
Sequence: | 6; |
Isoform 4 expressed at high levels by CD8(+) dendritic cells (DCs), and at low levels by plasmacytoid DCs but not by other hematopoietic cells.
The CLEC9A marker is a molecule that resembles a surface lectin that is found on dendritic cells (DCs). Its function in cross-priming CTLs and in the elimination of tumors could make it a viable option for adjuvants and vaccines. This Boster Bio article will provide additional information on this marker. This article will provide information on how CLEC9A can be used to determine if an adjuvant or vaccine is effective.
The gene mClec9A was the source of mClec9A. Its primary function is to be able to bind mClec9a which is a c DC ligand, and a protein. The protein was manufactured in the Boster Bio lab using a standard solid phase strategy. After purification using reverse-phase high performance liquid chromatography (RP-HPLC) and mass spectrometry the peptides were identified and identified. The peptides were also mutated through an insilico procedure. A synthetic peptide was made from mClec9a. It was linked to OVA257-264, a carboxyl terminal GGGKbiotin and SIIN
CLEC9a does not just bind mClec9a and mClec9a but also regulates the immune response. Through stimulating the production of ROS, CLEC9a inhibits the recruitment of neutrophils and other inflammatory cells to the sites of cellular damage. Syk is activated by the F-actin binding of mClec9a to the receptor mClec9a. It stimulates antigen cross-presentation.
The CBP-12 conjugated peptide vaccine targets Clec9a on DCs and activates the Syk pathway, thereby improving cross-presentation of antigens as well as CD8+ T cell function. CBP-12 conjugated peptide acts as a carrier for mClec9a expressed DCs and triggers IL-21 release. It has antitumor properties and reduces the release chemical mediators of inflammation.
Surface proteins that resemble lectins recognize certain molecular patterns. These patterns can be self-generated or obtained from other organisms. In animals the DECTIN-1 cluster is a source of C-type lectin-like receptors. These molecules are highly conserved among species and play a crucial role in the immune response. These receptors are found in natural killer cells' telomeric region.
These molecules share many characteristics with mammalian C-type lectin-like receptors. They also appear to lack a transmembrane domain (CTLD) and an area of transmembrane. These similarities point to the fact that the proteins are closely connected to C-type lectin-like molecule. The study suggests that mClec9A could be a surface lectin-like molecule that is essential for the immune system.
The CBP-12 conjugated antigen is known to improve the therapeutic efficacy of radiotherapy. CLEC9A/OVA has significantly reduced neutrophils that invaded the tumor in the mouse model. CLEC9A-OVA vaccine on DCs also increases the ability to produce anti-inflammatory Cytokines by CD8+ T cells, thereby increasing immunity-mediated tissue injury.
A recent study published in the Journal of Immunology suggests that the CLEC9A marker is expressed on DC precursors. This marker is expressed by a small amount of cells, and could be the precursors for intestinal DCs. However, these findings are not yet conclusive. Up to now, it was difficult to identify the role played by CLEC9A in DC development. More research is required to determine its exact purpose and the biological significance.
Several types of DCs are present in the body, and the expression of the CLEC9A marker on these cells may assist in determining the most suitable method of treatment. This marker is found on cDCs located in a variety of tissues. DCs that are found in blood are thought to be the most diverse of cell kinds in the body and they could be differentiated by distinct types of phenotypes.
In addition to their capability to help in the fight against inflammation, DCs have important roles in the immune response against cancer. DCs' levels in blood can be used to predict the progression of cancer. Patients with advanced stages of cancer are more likely to have lower DC levels. But, despite their role of DCs in promoting cancer immunity, DCs also serve as crucial factors in infiltrating tumors by creating soluble substances that regulate the tumor's microenvironment. Furthermore, DCs act as a precursor for T cells and increase CTL activity. In addition to these functions, cDC1 growth has been linked with increased responses to therapy and survival.
Several other markers have been identified as markers of DCs. FLT3 has been identified as an indicator for MDP and CSF1R (and ITGAX) have been identified as pre-DC markers. In addition, mDCs have an endocrine subset known as pre-cDC. The two types of cells differ in their functions, however the DC-DTR22 and zDC CRE24 mice can be useful in studying DC development.
A new study suggests that CLEC9A is also expressed on DCs in other tissues, such as the skin and intestine. While DCs are found in all organs and tissues, CLEC9A is expressed in the liver, intestines, lung, and lung. These cells play an essential role during the development of many diseases, like cancer and are involved in immune system-related innate reactions. It is therefore crucial to understand how these cells work.
Vaccine development is currently focused on the TCR receptor CLEC9A (also called DNGR1). This protein is able to recognize dead cells and delivers Ag to endosomes. It also regulates cross-priming for CD8+ T cells. When delivered to DCs that are CD8a+/CD103+ it stimulates potent antiviral and immune innate responses.
The hemopoietic system's DCs are where the majority of mClec9A proteins are expressed. mAb10B4 was not able to stain cells other than DCs. This suggests that the protein is restricted to DCs. Boster Bio is committed to developing vaccines and hopes to develop effective vaccines targeting TCR. The company is seeking approval from the FDA for their CLEC9A antibody to speed up the development of vaccines for immunological conditions.
The Clec9A-lectin is a dendritic cell-re molecule that has an human ortholog. Researchers have identified the protein Clec9A through gene expression profiling of mouse DC types and determined its structure. Surface staining revealed that Clec9A was expressed primarily by plasmacytoid subtypes and CD8+ DC subtypes.
The Clec9A mAbs targeted DCs and led to increased antibody responses even without adjuvants. It also improved the weak response of mice to ovalbumin and rat Ig, even though the dose was 1000-fold less than the free Ag. The Clec9A-targeted Ags were capable of activating a broad range of Ig isotypes, which suggests a potential for increased effectiveness of the vaccine.
To study the mechanism by that CLEC9A binds to peptides, a PEP-FOLD-like protein was designed to mimic the W Peptide. This model revealed that Clec9a binding was inhibited at seven of its nine residues (W250 and D248). This suggests that Clec9a is specifically bound by PEP-FOLD-derived proteins.
The CLEC9A CTLD peptide was isolated from the bone marrow cells of mice. The activation and cross-presentation of Clec9a+ DCs was enhanced by peptides bound the peptide WH. The peptide could be an effective therapeutic target for cancer immunotherapy. Researchers have tested the Clec9a CTLD peptide on two mouse strains: OT-1 mice and C57Bl/6J mice. The ethics committee of Zhengzhou University approved all animal research.
The discovery of CLEC9A as a possible adjuvant target has significant implications for clinical development. It has been established that mice with CLEC9A receptors are capable of generating strong CTL responses. The receptor is found in both mammals and humans which makes it a perfect candidate for clinical testing. Therefore, a better understanding of the way CLEC9A regulates immune responses is crucial to developing more efficient immunotherapy.
The cell molecule Clec9A can influence the outcome of the immune response. Thus targeting this molecule can eliminate biases in the presentation of Ag by DC subsets. CLEC9A is also expressed on DC that possess CD8a and pDC but not on other types of cell. The protein possesses an intracellular hemITAM molecule and an extracellular C-type lectin-like.
Additionally the agonists chemically defined by CLEC9A could also enhance antibody responses. Chemically defined adjuvants perform better than traditional adjuvants such as alum. There are many adjuvants. There are a myriad of combinations and agonists. There are numerous adjuvants on the market today, including curdlan , and synthetic double-strandedRNA.
The phase II study has revealed that Clec9a can be used as a target for tumor vaccines. Clec9a-targeting adjuvants can be effective in increasing CTL production. They also enhance the effectiveness of vaccines when they're infused by using an antigen that targets Clec9a. These results are very positive and emphasize the importance of focusing on CLEC9A during clinical trials.
PMID: 18408006 by Huysamen C., et al. CLEC9A is a novel activation C-type lectin-like receptor expressed on BDCA3+ dendritic cells and a subset of monocytes.
PMID: 18497879 by Sancho D., et al. Tumor therapy in mice via antigen targeting to a novel, DC-restricted C-type lectin.