The Introduction of CCR


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The Introduction of CCR

Overview of some antibodies:

1. CCR2 Antibody (1D9)

CCR2is a receptor for the C-C chemokines that can bind MCP-1, MCP-2, MCP-3, MCP-4 and MCP-5. CCR2 processes and cellular responses mediated by CCR2 as well, involvings in rejection of transplanted grafts.

2. CCR6 Antibody (MSM-R606)

This antibody against human CCR6 can be used to detect the presence of CCR6 on cells, so it can also be used to cut down the effects of over-stimulation of CCR6 in various conditions and disorders, including cancers.

3. CCR8 Antibody

This product is a mouse antibody specific for CCR8, which can be used for various applications such as FC.

So, today let's learn about the CCR.

To play a biological role, chemokines must be combined with corresponding receptors. Chemokine receptor belongs to G protein coupled receptor, which has 7 α - helix membrane area structures, rich in hydrophobic amino acids. It is mainly expressed in various leukocyte subsets from bone marrow, and also in epithelial cells, vascular endothelial cells, nerve cells and other cell types. Among them, 11 CCR subsets (CCR1-CCR11) have been cloned.


CCR1 responds to a variety of human CC chemokines, including calcium mobilization, adenylate cyclase inhibition, extracellular acidification and increased chemotaxis. CCR1 has been cloned from several species and genera, such as rhesus monkey, rabbit, mouse and rat, and there is a high degree of sequence homology between these sequences. The similarity between human and rhesus monkey is 87%.Most of the significant features of human CCR1 sequence are conservative, and the changes are mainly limited to N-terminal and extracellular ring, which may be involved in ligand binding. Through the study of targeted gene destruction and effective CCR1 antagonists, the physiological and pathophysiological functions of CCR1 are provided.


CCR2 cDNA can encode CCR2A and CCR2B proteins. CCR2B is the main expression form and plays a role in chronic inflammation, especially atherosclerosis and multiple sclerosis. CCR2 mRNA can be detected in monocytes, blood derived dendritic cells, natural killer cells and T lymphocytes, but not in neutrophils or eosinophils.Studies based on antibody showed that CCR2b was expressed in monocytes, activated memory T cells, B cells and basophils. CCR2, through binding with ligands, produces many biological signals, including the inhibition of adenylate cyclase, the mobilization of intracellular calcium and the increase of cell chemotaxis. CCR2 has been cloned from many species, including mice, rats and rhesus monkeys, of which the sequence was highly homologous and showed the same 78-95% amino acids as human CCR2. CCR2 specifically binds to MCP-1 and MCP-3 with high affinity. CCR2 mRNA expression was detected in induced peritoneal macrophages and several mouse organs.

The results showed that CCR2 plays an important role in the formation of atherosclerosis.


CCR3 is mainly detected in eosinophils and functions essentially in regulating the migration of these cells. Recent studies have shown that CCR3 neutralizes monoclonal antibody 7b11 and blocks the binding of eosinophil activating chemokine to CCR3 transfectors or eosinophils. CCR3 may be more involved in Th2 response and play an important role in allergic reactions, including asthma and atopic dermatitis.CCR3 is shown as a common receptor of HIV-1 by several groups and expressed in microglia of brain, which may potentially promote HIV-1 infection of AIDS, leading to AIDS, dementia and other diseases. In addition, it showed that CCR3 can be expressed on dendritic cells and may induce HIV-1 infection.


CCR4 was originally cloned from human basophil leukemia cell line library. Many studies have shown that CCR4 is a selective marker of Th2 lymphocytes and up regulated by T cell receptor. CCR4 can be detected in the memory T cells in the blood and participate in the systemic lymphocyte immune response. CCR4 may play a role in the pathophysiology of liver injury.


In addition to working as chemokine receptor, CCR5 may also play a role in the pathology of HIV-1 key cells entering the co-receptor.The deletion of 32 base pairs in human CCR5 gene (ccr5-32) results in amino acid shift and serious truncation. CCR5 can also be inactivated by targeting the modified CC chemokine to endoplasmic reticulum to block the surface expression of the newly synthesized CCR5. CCR5 ligands include gp120 envelope glycoprotein from M-tropic HIV-1 strain, which requires CD4 binding.CCR5 antagonists, like Met-RANTES and AOP RANTES, are N-terminal modified RANTES proteins that are effective CCR5 antagonists and inhibit M-tropic HIV-1 infection in macrophages and lymphocytes. Although CCR5 expresses in Th1 and Th2 lines, yet it is not expressed in several Th2 clones, and its expression is significantly influenced by IL-2. These results indicate that the flexible program of chemokine receptor gene expression can control the tissue-specific migration of effector T cells and play a role.


CCR6 is mainly expressed in spleen, lymph nodes, appendix and fetal liver. CCR6 mRNA is detected in lymphocytes (CD4 (+) and CD8 (+) T cells and B cells), but not in natural killer cells, monocytes or granulocytes. The expression of CCR6 mRNA in CD4 (+) and CD8 (+) T cells was strongly upregulated by IL-2.CCL20 (LARC), produced by activated macrophages, dendritic cells and endothelial cells, is the only high affinity ligand and effective activator of CCR6. The homology of mouse CCR6 with human amino acid reaches about 76%. CCR6 plays an important role in the physiology and function of dendritic cells. CCR6 and CCL20 are up-regulated in psoriasis, which may be involved in the immune pathogenesis of the disease, and may play a role in T cell recruitment into the skin of psoriasis.


CCR7works essentially in the transport of T lymphocytes and dendritic cells. The expression of CCL19 mRNA is the strongest in thymus and lymph nodes. It was found that the recombinant CCL19 protein binds CCR7 with high affinity and induces calcium mobilization and chemotaxis.CCL19, a highly specific ligand of CCR7, gets expressed in activated B and T lymphocytes, and is strongly upregulated in T cells or B cells infected with EB virus and herpes virus. Therefore, CCR7 may affect the migration and homing of normal lymphocytes and the pathophysiology of lymphocytes infected with these herpes viruses.CCL19 and CCR7 may be involved in the transportation of a wide range of lymphocytes, especially activated T cells. The signals sent through CCR7 have a strong positive effect on the growth of HIV.


CCR8, formerly known as orphan receptor ter1, chemr1 or ckr-l1, is highly expressed in thymus and spleen, and is almost undetectable in peripheral blood lymphocytes. CCR8 information is also abundant in some NK and T cell lines and Th2 lymphocytes.


CCR10 is highly expressed in human testis and small intestine, but low in other tissues. CCR10 is expressed at a low level in the small intestine, colon, lymph nodes, thymus and spleen, which can be expressed by melanocytes, dermal fibroblasts and dermal microvascular endothelial cells, and can also be produced by T cells and skin derived Langerhans cells. In conclusion, these studies suggest that CCR10 has potential roles in skin homeostasis and inflammatory response.


CCR11 is mainly expressed in heart, small intestine and lung, but not in peripheral blood, which can also be expressed in parenchymal cells, but its role is not clear. CCR11 is very important for the normal development of heart, small intestine and brain. In addition, the chemokine receptor US28 encoded by the virus may play a part in the aggravation of cytomegalovirus in angiopathy.

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