immune response

RIG-I Protein, Human, Recombinant (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 53.3 kDa and the accession number is O95786.

Calmodulin (CaM) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the binding of Ca2+ is required for the activation of Calmodulin. Once bound to Ca2+, Calmodulin acts as part of a calcium signal transduction pathway by modifying its interactions with various target proteins such as kinases or phosphatases. Calmodulin is a small, highly conserved protein that is 148 amino acids long. The protein has two approximately symmetrical globular domains each containing a pair of EF-hand motifs (the N- and C-domain) separated by a flexible linker region for a total of four Ca2+ binding sites. Calmodulin mediates many crucial processes such as inflammation, metabolism, apoptosis, smooth muscle contraction, intracellular movement, short-term and long-term memory, and the immune response. Calmodulin is expressed in many cell types and can have different subcellular locations, including the cytoplasm, within organelles, or associated with the plasma or organelle membranes, but it is always found intracellularly.

B7 Homolog 4 (B7-H4) is glycosylated member of the B7 family of immune costimulatory proteins. Mature human B7-H4 consists of a 235 amino acid (aa) extracellular domain (ECD) with two Ig-like V-type domains, a 21 aa transmembrane segment, and a 2 aa cytoplasmic tail. It is widely expressed, including in kidney, liver, lung, pancreas, placenta, prostate, spleen, testis and thymus. B7-H4 negatively regulates T-cell-mediated immune response by inhibiting T-cell activation, proliferation, cytokine production and development of cytotoxicity. When expressed on the cell surface of tumor macrophages, plays an important role, together with regulatory T-cells (Treg), in the suppression of tumor-associated antigen-specific T-cell immunity. It also involved in promoting epithelial cell transformation.

Butyrophilin subfamily 3 member A2, also known as BT3.2, BTF3, BTF4 and BTN3A2, is a single-pass type I membrane protein. It is a member of the butyrophilin (BTN) family and the immunoglobulin (IG) superfamily. Mature human BTN3A2 is a 305 amino acid (aa) glycoprotein. It contains a 219 aa extracellular region with one V-type Ig-like domain, and a 65 aa cytoplasmic tail. The cytoplasmic region undergoes phosphorylation on two serines. There are three potential splice forms. BTN3A2 is postulated to be expressed on immune-related cells, as it has a structural similarity to MHC and CD80/CD86 molecules. It plays a role in T-cell responses in the adaptive immune response and inhibits the release of IFNG from activated T-cells.

Fcgr4, also known as CD16-2, is one of the receptors for Fc region of IgG which involve in immune responses. Fcgr4 mainly functions in cellular response to lipopolysaccharide, NK T cell proliferation, regulation of sensory perception of pain, wound healing etc. Three groups are included for Fc γ receptors (FcR), and they are Fc γ RI (CD64), Fc γ RII (CD32), and Fc γ RIII (CD16). Among these, CD64 possess high affinity even for monomeric IgG, while CD32 and CD16 display a relative lower affinity for IgG. Genes encodes these receptors are diverse differing by species and cell types. The aggregation of FcR having immunoreceptor tyrosine-based activation motifs (ITAMs) activates sequentially src family tyrosine kinases and syk family tyrosine kinases that connect transduced signals to common activation pathways shared with other receptors. FcR with ITAMs elicit cell activation, endocytosis, and phagocytosis. Fcgr4 belongs to Fc γ RIII (CD16) group.

Integrin β-1 (ITGB1) belongs to the integrin β chain family. Integrin family members are membrane receptors involved in cell adhesion and recognition in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic diffusion of tumor cells. ITGB1 is an integrin unit associated with very late antigen receptors, which contains one VWFA domain. It is known to conjoin with α-3 subunit to create α3β1 complex that reacts to such molecules as netrin-1 and reelin.

Lysosomal associated membrane protein 1 (LAMP1) is an approximately 120 kDa transmembrane glycoprotein that is a major protein component of lysosomal membranes. Mature mouse LAMP1 consists of a 346 amino acid (aa) intralumenal domain (ECD), a 24 aa transmembrane segment, and a 12 aa cytoplasmic tail. Its lumenal domain is organized into two heavily N-glycosylated regions separated by a Ser/Pro-rich linker that carries a minor amount of O-linked glycosylation. Within the lumenal domain, mouse LAMP1 shares approximately 64% and 82% aa sequence identity with human and rat LAMP1, respectively. The sorting of LAMP1 to lysosomes relies on a tyrosine motif in the cytoplasmic tail. In cytotoxic T cells and mast cells, LAMP1 is expressed in the membranes of intracellular granules that contain effector molecules such as perforin, granzymes, eicosanoids, and histamine. A glycoform of LAMP1 known as M150 is expressed on the surface of activated macrophages where it promotes T cell co-stimulation and a Th1 biased immune response. Exposure of epithelial cells to pathogenic Neisseria bacteria induces the redistribution of LAMP1 to the cell surface where it can be cleaved by the Neisseria IgA1 protease.

Pentraxin-related protein PTX3, also known as Tumor necrosis factor-inducible gene 14 protein (TSG-14), belongs to the pentraxin family. PTX3 plays a role in the regulation of innate resistance to pathogens, inflammatory reactions, possibly clearance of self-components and female fertility. It’s subunit is a disulfide-linked homooctamer that binds to C1q. PTX3 concentration is elevated in the joint fluid of patients with rheumatoid arthritis (RA), indicating that PTX3 may be a potential mediator of immune response. PTX3 may also function in the regulation of the uptake and clearance of apoptotic cells by dendritic cells. An in vivo study showed that PTX3 transgenic mice are more resistant to sepsis and endotoxemia compared to wild-type during inflammatory injury.

Programmed cell death protein 1, also known as PD-1 and CD279 , is a protein found on the surface of cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self tolerance by suppressing T cell inflammatory activity. PD-1 Protein, Canine, Recombinant (aa 25-170, hFc) is expressed in HEK293 mammalian cells with C-hFc tag. The predicted molecular weight is 43.00 kDa and the accession number is A0A090BAM7.

Bactericidal/permeability-increasing fold containing family A, member 1 (BPIFA1) is a secretory protein found in human upper aerodigestive tract mucosa. This innate material is secreted in mucosal fluid or found in submucosal tissue in the human soft palate, lung, uvula, and nasal cavity. BPIFA1 is a critical component of the innate immune response that prevents upper airway diseases.

IFN gamma, also known as IFNG, is a secreted protein that belongs to the type II interferon family. IFN gamma is produced predominantly by natural killer and natural killer T cells as part of the innate immune response, and by CD4 and CD8 cytotoxic T lymphocyte effector T cells once antigen-specific immunity develops. IFN gamma has antiviral, immunoregulatory, and anti-tumor properties. IFNG, in addition to having antiviral activity, has important immunoregulatory functions, it is a potent activator of macrophages and has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons. The IFNG monomer consists of a core of six α-helices and an extended unfolded sequence in the C-terminal region. IFN gamma is critical for innate and adaptive immunity against viral and intracellular bacterial infections and tumor control. Aberrant IFN gamma expression is associated with some autoinflammatory and autoimmune diseases. The importance of IFN gamma in the immune system stems in part from its ability to inhibit viral replication directly, and most importantly from its immunostimulatory and immunomodulatory effects. IFNG also promotes NK cell activity.

E3 ubiquitin ligase required to protect genome stability in response to replication stress. Acts as a key regulator of interstrand cross-link repair, which takes place when both strands of duplex DNA are covalently tethered together, thereby blocking replication and transcription. Controls the choice between the two pathways of replication-coupled interstrand-cross-link repair by mediating ubiquitination of MCM7 subunit of the CMG helicase complex. Short ubiquitin chains on MCM7 promote recruitment of DNA glycosylase NEIL3. If the interstrand cross-link cannot be cleaved by NEIL3, the ubiquitin chains continue to grow on MCM7, promoting the unloading of the CMG helicase complex by the VCP/p97 ATPase, enabling the Fanconi anemia DNA repair pathway. Only catalyzes ubiquitination of MCM7 when forks converge. Also involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis: promotes ubiquitination of DPCs, leading to their degradation by the proteasome. Has also been proposed to play a role in promoting translesion synthesis by mediating the assembly of 'Lys-63'-linked poly-ubiquitin chains on the Y-family polymerase POLN in order to facilitate bypass of DNA lesions and preserve genomic integrity. The function in translesion synthesis is however controversial. Acts as a regulator of the spindle assembly checkpoint. Also acts as a negative regulator of innate immune signaling by inhibiting activation of NF-kappa-B mediated by TNF. Negatively regulates TLR3/4- and RIG-I-mediated IRF3 activation and subsequent IFNB1 production and cellular antiviral response by promoting 'Lys-48'-linked polyubiquitination of TNK1 leading to its proteasomal degradation.

DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic core component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. Forms the polymerase active center together with the second largest subunit. A single-stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol III. A bridging helix emanates from RPC1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol III by acting as a ratchet that moves the RNA-DNA hybrid through the active site by switching from straight to bent conformations at each step of nucleotide addition. Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses. Acts as nuclear and cytosolic DNA sensor involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts, such as Epstein-Barr virus-encoded RNAs (EBERs) induce type I interferon and NF- Kappa-B through the RIG-I pathway.

Key element of the urea cycle converting L-arginine to urea and L-ornithine, which is further metabolized into metabolites proline and polyamides that drive collagen synthesis and bioenergetic pathways critical for cell proliferation, respectively; the urea cycle takes place primarily in the liver and, to a lesser extent, in the kidneys.; Functions in L-arginine homeostasis in nonhepatic tissues characterized by the competition between nitric oxide synthase (NOS) and arginase for the available intracellular substrate arginine. Arginine metabolism is a critical regulator of innate and adaptive immune responses. Involved in an antimicrobial effector pathway in polymorphonuclear granulocytes (PMN). Upon PMN cell death is liberated from the phagolysosome and depletes arginine in the microenvironment leading to suppressed T cell and natural killer (NK) cell proliferation and cytokine secretion. In group 2 innate lymphoid cells (ILC2s) promotes acute type 2 inflammation in the lung and is involved in optimal ILC2 proliferation but not survival. Plays a role in the immune response of alternatively activated or M2 macrophages in processes such as wound healing and tissue regeneration, immune defense against multicellular pathogens and parasites, and immune suppression and allergic inflammation; the regulatory outcome seems to be organ specific. In tumor-infiltrating dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) plays a role in suppression of T cell-mediated antitumor immunity.

Plays a role in the escape of host innate immune response by promoting the degradation of host EIF2AK2/PKR and inhibiting host transcription. Cytoplasmic NSs interacts with host FBXW11 to degrade PKR whereas nuclear pool binds to host FBXO3 to target TFIIH subunit GTF2H1 for proteasomal degradation. Forms filaments in the nucleus that may sequester NSs binding partners, causing cell cycle arrest. Rift valley fever virus (RVFV) (strain ZH-548 M12) Non-structural protein S (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 37.3 kDa and the accession number is P21698.

CCL16, a chemokine poorly characterized at the functional level. Human CCL16 is a member of the CC family, and its gene maps to human chromosome 17q. In the mouse, only a pseudogene has been identified to date. CCL16 is a functional ligand for CCR1, CCR2, CCR5, and CCR8. Recombinant CCL16 demonstrated chemotactic activity on human monocytes and lymphocytes. Based on the ability of human chemokines to exert activity on and bind to murine receptors, the TSA mouse adenocarcinoma cell line was transfected with human CCL16 cDNA and, in comparison with other cytokines, was shown to be the faster inducer of systemic immune response due to massive, prompt infiltration of leukocytes.Cancer ImmunotherapyImmune CheckpointImmunotherapyTargeted Therapy

Trem-like transcript 1 protein, also known as Triggering receptor expressed on myeloid cells-like protein 1, TREML1 and TLT-1, is a cytoplasm and single-pass type I membrane protein. TREML1 / TLT-1 is expressed exclusively in platelets and megakaryocytes (MKs) and that its expression is up-regulated dramatically upon platelet activation. It is a receptor that may play a role in the innate and adaptive immune response. TREML1 / TLT-1 contains the characteristic single V-set immunoglobulin (Ig) domain, its longer cytoplasmic tail is composed of both a proline-rich region and an immune receptor tyrosine-based inhibitory motif, the latter known to be used for interactions with protein tyrosine phosphatases. The triggering receptors expressed on myeloid cells (TREMs) have drawn considerable attention due to their ability to activate multiple cell types within the innate immune system, including neutrophils, monocyte / macrophages, and dendritic cells, via their association with DAP12. TREML1 / TLT-1 is prepackaged, along with CD62P, into both MK and platelet alpha-granules. Differences in thrombin-induced redistribution of CD62P and TREML1 indicate that TREML1 is not simply cargo of alpha-granules but may instead regulate granule construction or dispersal. TREML1 / TLT-1 does not function to inhibit members of the TREM family but instead may play a role in maintaining vascular hemostasis and regulating coagulation and inflammation at sites of injury.

Chondrocyte protein 39 (YKL-39), also known as Chitinase 3-like 2 (CHI3L2), is a secretory protein of articular chondrocytes belonging to the glycosyl hydrolase 18 family. Its highest expression is in chondrocytes, followed by synoviocytes, lung and heart. YKL-39/CHI3L2 is not detected in spleen, pancreas, and liver. YKL-39/CHI3L2 may also be expressed in developing brain and placenta. YKL-39/CHI3L2, a cartilage-related protein, is found to induce arthritis accompanied by pathologic changes in bone and cartilage. A better understanding of the immune response against cartilage-related components including YKL-39 may help to elucidate the pathological processes of arthritic disorders. Upregulation of YKL-39/CHI3L2 in osteoarthritic cartilage suggests that YKL-39/CHI3L2 may be a more accurate marker of chondrocyte activation than YKL-40, although it has yet to be established as a suitable marker in synovial fluid and serum. The decreased expression of YKL-40 by osteoarthritic chondrocytes is surprising as increased levels have been reported in rheumatoid and osteoarthritic synovial fluid, where it may derive from activated synovial cells or osteophytic tissue or by increased matrix destruction in the osteoarthritic joint. YKL-39 and YKL-40 are potentially interesting marker molecules for arthritic joint disease because they are abundantly expressed by both normal and osteoarthritic chondrocytes.

CCL11 or chemokine (C-C motif) ligand 11 is a member of the chemokine (C-C motif) ligand family. Chemokin (C-C motif) ligand 11 is a member of the chemokine family. There are four members of the chemokine family: C-C kemokines, C kemokines, CXC kemokines and CX3C kemokines. The C-C kemokines have two cysteines nearby the amino terminus. There have been at least 27 distinct members of this subgroup reported for mammals, called C-C chemokine ligands (CCL)-1 to 28. Chemokines are a family of small chemotactic cytokines, or proteins secreted by cells. They share the same structure similarities such as small size, and the presence of four cysteine residues in conserved locations in order to form their 3-dimensional shape. Some of the chemokines are considered pro-inflammatory which can be induced to recruit cells of the immune system to a site of infection during an immune response, while others are considered homeostatic and are implied in controlling the migration of cells during normal processes of tissue maintenance and development. CCL11 is implicated in allergic responses through selectively recruiting eosinophils by inducing their chemotaxis. The effects of CCL11 are mediated by its binding to chemokine receptor. Increased CCL11 levels in blood plasma are associated with aging in mice.

Mitogen-activated protein kinase 9 (MAPK9), also well known as c-Jun N-terminal kinase (JNK2), is a member of the MAP kinase subfamily belonging to the protein kinase superfamily. MAPK9 responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating some transcription factors, such as c-Jun and ATF2. The crystal structure of human JNK2 complexed with an indazole inhibitor by applying a high-throughput protein engineering and surface-site mutagenesis approach. A novel conformation of the activation loop is observed, which is not compatible with its phosphorylation by upstream kinases. This activation inhibitory conformation of JNK2 is stabilized by the MAP kinase insert that interacts with the activation loop in an induced-fit manner. It suggests that the MAP kinase insert of JNK2 plays a role in the regulation of JNK2 activation, possibly by interacting with intracellular binding partners. JNK2 deficiency leads to reduced c-Jun degradation, thereby augmenting c-Jun levels and cellular proliferation, and suggests that JNK2 is a negative regulator of cellular proliferation in multiple cell types. JNK2 prevents replicative stress by coordinating cell cycle progression and DNA damage repair mechanisms. JNK2 blocks the ubiquitination of tumor suppressor p53, and thus increases the stability of p53 in nonstressed cells. JNK2 negatively regulates antigen-specific CD8+ T cell expansion and effector function, and thus selectively blocking JNK2 in CD8+ T cells may potentially enhance the anti-tumor immune response. Lack of JNK2 expression was associated with higher tumor aneuploidy and reduced DNA damage response. Additionally, the JNK2 protein could be a novel therapeutic target in dry eye disease and may provide a novel target for the prevention of vascular disease and atherosclerosis.

C12orf53 is mainly expressed in adult brain and cerebellum. It also can be detected in fetal brain and virtually no expression in spleen, heart, kidney, liver and dorsal ganglion relative to brain. C12orf53 acts as a ligand for PILRA in neural tissues, where it may be involved in immune regulation. Chromosome 12 encodes over 1,100 genes within 132 million bases. A number of skeletal deformities are linked to chromosome 12 including hypochondrogenesis, achondrogenesis and Kniest dysplasia. Noonan syndrome, which includes heart and facial developmental defects among the primary symptoms, is caused by a mutant form of PTPN11 gene product, SH-PTP2. Chromosome 12 is also home to a homeobox gene cluster which encodes crucial transcription factors for morphogenesis, and the natural killer complex gene cluster encoding C-type lectin proteins which mediate the NK cell response to MHC class I interaction.

Members of the CLIC family are largely soluble proteins that possess the intriguing property of spontaneous insertion into phospholipid bilayers to form integral membrane ion channels. Chloride intracellular channel 1 (CLIC1), a newly discovered member of the chloride channel protein family, has been implicated in multiple human cancers. CLIC1 is a Chloride Intracellular Ion Channel protein that exists either in a soluble state in the cytoplasm or as a membrane bound protein. CLIC1 acts as a putative oncogene in pancreatic cancer and may represent a novel diagnostic and therapeutic target for pancreatic cancer. Intracellular chloride channel protein 1 (CLIC1) participates in inflammatory processes by regulating macrophage phagosomal functions such as pH and proteolysis. CLIC1 is a novel therapeutic target to help reduce the adaptive immune response in autoimmune diseases. The expression of CLIC1 might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of pancreatic ductal adenocarcinomas. Intracellular chloride channel 1 (CLIC1), a novel metamorphic protein, acts as a sensor of cell oxidation and is involved in inflammation.

Programmed cell death protein 1(PDCD1) is a single-pass type I membrane protein and contains 1 Ig-like V-type domain. PD-1 is a member of the extended CD28/CTLA-4 family of T cell regulators. PDCD1 inhibits the T-cell proliferation and production of related cytokines including IL-1, IL-4, IL-10 and IFN-γ by suppressing the activation and transduction of PI3K/AKT pathway. In addition, coligation of PDCD1 inhibits BCR-mediating signal by dephosphorylating key signal transducer. PDCD1 has been suggested to be involved in lymphocyte clonal selection and peripheral tolerance, and thus contributes to the prevention of autoimmune diseases. As a cell surface molecule, PDCD1 regulates the adaptive immune response. Engagement of PD-1 by its ligands PD-L1 or PD-L2 transduces a signal that inhibits T-cell proliferation, cytokine production, and cytolytic function.

B- and T-Lymphocyte Attenuator (BTLA) is a single-pass type I membrane protein containing 1 Ig-like V-type (immunoglobulin-like) domain. BTLA expression is induced during activation of T cells, and BTLA remains expressed on Th1 cells but not Th2 cells. Like PD1 and CTLA4, BTLA interacts with a B7 homolog, B7H4. However, unlike PD-1 and CTLA-4, BTLA displays T-Cell inhibition via interaction with tumor necrosis family receptors (TNF-R), not just the B7 family of cell surface receptors. BTLA is a lymphocyte inhibitory receptor that inhibits lymphocytes during immune response. BTLA also is a ligand for tumor necrosis factor (receptor) superfamily, member 14 (TNFRSF14), also known as herpes virus entry mediator (HVEM). BTLA-HVEM complexes negatively regulate T-cell immune responses.

Tumor necrosis factor receptor superfamily member 19L (TNFRSF19L), also known as Receptor expressed in lymphoid tissues and RELT, is a member of the TNF-receptor superfamily. TNFRSF19L is a single-pass type membrane protein and contains one TNFR-Cys repeat. TNFRSF19L is highly expressed in spleen, lymph node, thymus, peripheral blood leukocytes, bone marrow and fetal liver. It has been shown TNFRSF19L activates the NF-kappaB pathway and selectively binds TNF receptor-associated factor 1 (TRAF1). TNFRSF19L is capable of stimulating T-cell proliferation in the presence of CD3 signaling, which suggests its regulatory role in immune response.

Activated leukocyte cell adhesion molecule (ALCAM), also named as CD166 and MEMD, is a typeI transmembrane glycoprotein of immunoglobulin superfamily, which mediates homotypic and heterotypic interactions between cells. ALCAM interacts with high affinity with CD6 molecule but weaker homotypic (ALCAM–ALCAM) interactions have also been described. ALCAM–CD6 interactions play an important role in the maintenance of T cell activation, proliferation as well as in formation of immune synapse between antigen-presenting cell and lymphocytes. ALCAM is expressed on a wide variety of cells, particularly on activated lymphocytes, dendritic cells and monocytes, and on various epithelial cell types. It is also involved in multiple processes including embryogenesis, hematopoiesis, angiogenesis, and immune response. While expressed in a wide variety of tissues, ALCAM is usually restricted to subsets of cells in most adult tissues. Recently studies showed ALCAM has prognostic relevance in several human carcinomas, and it has been used as a biomarker for several tumor entities, including melanoma, gynecologic, urologic, and gastrointestinal cancers.

Interleukin-4 receptor subunit alpha(IL-4RA), alos known as Soluble IL-4 receptor subunit alpha, belongs to the type I cytokine receptor family and type 4 subfamily. It expressed in both Th1 and Th2 cells. It functions as receptor for both interleukin 4 and interleukin 13 and couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and chemokine and mucus production at sites of allergic inflammation. In certain cell types, IL-4RA can signal through activation of insulin receptor substrates, IRS1/IRS2. The functional IL4 receptor is formed by initial binding of IL4 to IL4R. Subsequently it recruits to the complex of the common gamma chain. In immune cells, IL-4RA creates a type I receptor. In non-immune cells, it forms a type II receptor with of IL13RA1. IL4R can also interact with the IL13/IL13RA1 complex to form a similar type II receptor and interacts with the SH2-containing phosphatases, PTPN6/SHIP1, PTPN11/SHIP2 and INPP5D/SHIP.

Mouse SLAM family member 9(Slamf9) is a single-pass type I membrane protein. The SLAMF9 gene encodes a member of the signaling lymphocytic activation molecule family. The encoded protein is a cell surface molecule that consists of two extracellular immunoglobulin domains, a transmembrane domain and a short cytoplasmic tail that lacks the signal transduction motifs found in other family members. The slamf9 protein may play a role in the immune response.

Cynomologous Cluster of Differentiation 80, also called B7-1, is a member of cell surface immunoglobulin superfamily.It is expressed on the surface of antigen-presenting cells including activated B cells, macrophages and dendritic cells.CD80 plays key, yet distinct roles in the activation of T cells. B7-1/CD80 and B7-2/CD86, together with their receptors CD28 and CTLA4, constitute one of the dominant co-stimulatory pathways that regulate T- and B- cell responses. CD80 is mostly expressed on the surface of antigen-presenting cells including activated B cells, macrophages and dendritic cells. Although both CTLA-4 and CD28 can bind to the same ligands, CTLA-4 binds to B7-1 and B7-2 with a 20-100 fold higher affinity than CD28 and is involved in the down-regulation of the immune response. CD80 is thus regarded as promising therapeutic targets for autoimmune diseases and various carcinomas.

C-type lectin domain family 2, member D (CLEC2D) is implicated in the immune response. Pre-eclampsia and HIV infection have opposing immune responses. The contrasting expression of CLEC2D in HIV infection and pre-eclampsia is demonstrative of the immunosuppressive and pro-inflammatory roles of the respective pathologies.

Interleukin-2(IL-2) is an interleukin, a type of cytokine signaling molecule in the immune system，belongs to the IL-2 family. It is a powerful immunoregulatory lymphokine produced by T-cells in response to antigenic or mitogenic stimulation. IL-2/IL-2R signaling is required for T-cell proliferation and other fundamental functions that are essential for the immune response. IL-2 stimulates growth and differentiation of B-cells, NK cells, lymphokine-activated killer cells, monocytes, macrophages and oligodendrocytes. New research has shown that IL-2 mutant reduced toxicity while being more potent at stimulating anti-tumor effector immune cells.

Interleukin-28B, also known as Cytokine Zcyto22, Interferon lambda-3, Interferon lambda-4, IFNL3, IFNL4, ZCYTO22 and IL28B, is a secreted cytokine which belongs to the IL-28/IL-29 family. IL-28 has also been shown to play a role in the adaptive immune response. IL28B has immunomodulatory activity and up-regulates MHC class I antigen expression. IL28B displays potent antiviral activity and antitumor activity. In addition, IL28B is a ligand for the heterodimeric class II cytokine receptor composed of IL10RB and IL28RA. The ligand/receptor complex seems to signal through the Jak-STAT pathway.

The Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV) is an enveloped, positive-stranded RNA viruses that can cause a severe respiratory disease. Its genome consists of a ∼30 kb linear, non-segmented, capped, polycistronic, polyadenylated RNA molecule, the first two-third of which is directly translated into two large polyproteins. These two polypeptides are processed into 16 non-structural proteins (nsps), forming the replicase complex, which is active in the cytoplasm in close association with cellular membranes. Nsp1 was proved to be able to suppress host gene expression by promoting host mRNA degradation and was involved in cellular chemokine deregulation. This virus evades the host innate immune response in part through the expression of its non-structural protein (nsp) 1, which inhibits both host gene expression and virus- and interferon (IFN)-dependent signaling. Thus, nsp1 is a promising target for drugs, as inhibition of nsp1 would make SARS-CoV more susceptible to the host antiviral defenses.

Toll-Interacting Protein (TOLLIP) is a member of the tollip family. TOLLIP localizes to the cytoplasm. It contains one C2 domain and one CUE domain. TOLLIP is an inhibitory adaptor protein for Toll-like receptors (TLR). The Toll-like receptors pathway is a part of the immune system that recognize structurally conserved molecular patterns of microbial pathogens, resulting in an inflammatory immune response. TOLLIP constitutes a complex with Tom1 to regulate endosomal transferring of ubiquitinated proteins. TOLLIP can negative regulate Toll-like receptors signaling, which may limit the production of proinflammatory mediators during the process of inflammation and infection.

Acts as a CD40 functional homolog to prevent apoptosis of infected B-lymphocytes and drive their proliferation. Functions as a constitutively active tumor necrosis factor receptor that induces the activation of several signaling pathways, including those of the NF-kappa-B family. LMP1 signaling leads to up-regulation of antiapoptotic proteins and provide growth signals in latently infected cells. Interacts with host UBE2I and subsequently affects the sumoylation state of several cellular proteins. For example, induces the sumoylation of host IRF7 thereby limiting its transcriptional activity and modulating the activation of innate immune responses. Inhibits also host IFN-alpha-stimulated STAT2 nuclear translocation and interferon-stimulated response element transcriptional activity by interacting with and inhibiting host TYK2.

A structural component of the cornified envelope of the stratum corneum involved in innate cutaneous host defense (Probable). Possesses defensin-like antimicrobial activity against a broad spectrum of Gram-positive and Gram-negative bacteria, both aerobic and anaerobic species. Upon inflammation, may regulate skin barrier repair by shaping cutaneous microbiota composition and immune response to bacterial antigens. LCE3A Protein, Human, Recombinant (His) is expressed in E. coli expression system with N-6xHis tag. The predicted molecular weight is 14.6 kDa and the accession number is Q5TA76.

Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation. Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation. Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death. Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus.

Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA. Required for double-strand break repair and V(D)J recombination. Also has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection. Binding to DNA may be mediated by XRCC6. The XRCC5-XRRC6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold. The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together. The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. The XRCC5-XRRC6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks. XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined. The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription. In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression. As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome. Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway.

Regulates pathways leading to the activation of NF-kappa-B and MAP kinases, and plays a central role in the regulation of B-cell survival. Part of signaling pathways leading to the production of cytokines and interferon. Required for normal antibody isotype switching from IgM to IgG. Plays a role T-cell dependent immune responses. Plays a role in the regulation of antiviral responses. Is an essential constituent of several E3 ubiquitin-protein ligase complexes. May have E3 ubiquitin-protein ligase activity and promote 'Lys-63'-linked ubiquitination of target proteins. Inhibits activation of NF-kappa-B in response to LTBR stimulation. Inhibits TRAF2-mediated activation of NF-kappa-B. Down-regulates proteolytic processing of NFKB2, and thereby inhibits non-canonical activation of NF-kappa-B. Promotes ubiquitination and proteasomal degradation of MAP3K14.

E3 ubiquitin-protein ligase whose activity is dependent on E2 enzymes, UBE2D1, UBE2D2, UBE2E1 and UBE2E2. Forms a ubiquitin ligase complex in cooperation with the E2 UBE2D2 that is used not only for the ubiquitination of USP4 and IKBKB but also for its self-ubiquitination. Component of cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes such as SCF(SKP2)-like complexes. A TRIM21-containing SCF(SKP2)-like complex is shown to mediate ubiquitination of CDKN1B ('Thr-187' phosphorylated-form), thereby promoting its degradation by the proteasome. Monoubiquitinates IKBKB that will negatively regulates Tax-induced NF-kappa-B signaling. Negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3. Mediates the ubiquitin-mediated proteasomal degradation of IgG1 heavy chain, which is linked to the VCP-mediated ER-associated degradation (ERAD) pathway. Promotes IRF8 ubiquitination, which enhanced the ability of IRF8 to stimulate cytokine genes transcription in macrophages. Plays a role in the regulation of the cell cycle progression. Enhances the decapping activity of DCP2. Exists as a ribonucleoprotein particle present in all mammalian cells studied and composed of a single polypeptide and one of four small RNA molecules. At least two isoforms are present in nucleated and red blood cells, and tissue specific differences in RO/SSA proteins have been identified. The common feature of these proteins is their ability to bind HY RNAs.2. Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma. Organizes autophagic machinery by serving as a platform for the assembly of ULK1, Beclin 1/BECN1 and ATG8 family members and recognizes specific autophagy targets, thus coordinating target recognition with assembly of the autophagic apparatus and initiation of autophagy. Acts as an autophagy receptor for the degradation of IRF3, hence attenuating type I interferon (IFN)-dependent immune responses. Represses the innate antiviral response by facilitating the formation of the NMI-IFI35 complex through 'Lys-63'-linked ubiquitination of NMI.

The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is mainly involved in the biosynthetic transport of proteins from the Golgi to the plasma membrane. Regulates, for instance, SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the plasma membrane. In parallel, it regulates the transport of TLR4, a toll-like receptor to the plasma membrane and therefore may be important for innate immune response. Plays also a specific role in asymmetric protein transport to the plasma membrane. In neurons, it is involved in axonogenesis through regulation of vesicular membrane trafficking toward the axonal plasma membrane. In epithelial cells, it regulates transport from the Golgi to the basolateral membrane. May play a role in the basolateral recycling pathway and in phagosome maturation. May play a role in endoplasmic reticulum dynamics and morphology controlling tubulation along microtubules and tubules fusion. Together with LRRK2, RAB8A, and RILPL1, it regulates ciliogenesis. When phosphorylated by LRRK2 on Thr-73, it binds RILPL1 and inhibits ciliogenesis.

Cysteine protease that plays an important role in the inhibition of host innate immune response. Degrades host elastin, fibrogen, fibronectin and kininogen. Blocks phagocytosis of opsonised S. aureus by neutrophils and monocytes by inducing their death in a proteolytic activity-dependent manner. Decreases surface expression of the 'don't eat me' signal CD31 on neutrophils. Cleaves host galectin-3/LGALS3, thereby inhibiting the neutrophil-activating ability of the lectin. Staphopain B Protein, S. aureus, Recombinant (GST) is expressed in E. coli expression system with N-GST tag. The predicted molecular weight is 46.9 kDa and the accession number is Q99V46.

CD28 (Cluster of Differentiation 28) is a disulphide-bonded glycoprotein belonging to the immunoglobulin (Ig) superfamily, and structurally consists of a single Ig V-like extracellular domain, a transmembrane domain and an intracellular domain. Mouse CD28 is constitutively expressed on the surface of all murine T cells and on developing thymocytes as disulfide-linked homodimers or as monomers. CD28 can binds the B7-1 and B7-2 ligand, and together perform important functions in the T and B cell response pathways. B7/CD28 family members, which can augment or antagonize T-cell receptor signaling, in the regulation of central and peripheral T-cell tolerance. CD28 is thus involved in T-cell activation, the induction of cell proliferation and cytokine production and promotion of T-cell survival.Cancer ImmunotherapyCo-stimulatory Immune Checkpoint TargetsImmune CheckpointImmune Checkpoint Detection: AntibodiesImmune Checkpoint Detection: ELISA AntibodiesImmune Checkpoint Detection: FCM AntibodiesImmune Checkpoint Detection: IHC AntibodiesImmune Checkpoint Detection: WB AntibodiesImmune Checkpoint TargetsImmunotherapyTargeted Therapy.

Granzymes are key components of the immune response that play important roles in eliminating host cells infected by intracellular pathogens. Several granzymes are potent inducers of cell death. A total of eight granzymes (A-G and M) have been identified in the mouse, but only five are known in humans (A, B, H, M, and granzyme 3), and granzyme H appears to be specifically human. Human granzyme H is a neutral serine protease that is expressed predominantly in the lymphokine-activated killer (LAK)/natural?killer (NK) compartment of the immune system. In adenovirus-infected cells in which granzyme B (gzmB) and downstream apoptosis pathways are inhibited, granzyme H directly cleaves the adenovirus DNA-binding protein (DBP), a viral component required for viral DNA replication. This virus demonstrated that gzmH directly induces an important decay in viral DNA replication. Interestingly, gzmH also cleaves the adenovirus 1K assembly protein, a major inhibitor of gzmB, and relieves gzmB inhibition. Granzyme H has a very high amino acid identity (>9%) with many portions of the granzyme B sequence, particularly near the amino terminus of the molecule despite performing a distinct enzymic function.

Trem-like transcript 2 protein, also known as Triggering receptor expressed on myeloid cells-like protein 2, TREML2 and TLT2, is a single-pass type I membrane protein that contains one Ig-like V-type (immunoglobulin-like) domain. TREML2 is detected in cultured B cells, T cell leukemia and monocyte leukemia. TREML2 is expressed constitutively on CD8 T-cells and induced on CD4 T-cells after activation. TREML2 is a cell surface receptor that may play a role in the innate and adaptive immune response. TREML2 acts as a counter-receptor for CD276 and interaction with CD276 on T-cells enhances T-cell activation. Murine B7-H3 is specifically bound to Triggering receptor expressed on myeloid cells (TREM)-like transcript 2 (TLT-2, TREML2). TREML2 was expressed on CD8(+) T cells constitutively and on activated CD4(+) T cells. Stimulation with B7-H3 transfectants preferentially up-regulated the proliferation and IFN-gamma production of CD8(+) T cells. Transduction of TREML2 into T cells resulted in enhanced IL-2 and IFN-gamma production via interactions with B7-H3. There may be a direct interaction between B7-H3 and TREML2 that preferentially enhances CD8(+) T cell activation.

BPIFB1, also known as LPLUNC1, belongs to the BPI/LBP/Plunc superfamily, plunc family. BPIFB1 may be involved in the innate immune response to bacterial exposure in the mouth, nasal cavities, and lungs. BPIFB1 is expressed in the upper respiratory tract and oral cavity, which may function in host defence. The expression of BPIF proteins is associated with CF lung disease in humans and mice. It is unclear if this elevation of protein production, which results from phenotypic alteration of the cells within the diseased epithelium, plays a role in the pathogenesis of the disease. BPIFB1 is an abundant, secreted product of goblet cells and minor mucosal glands of the respiratory tract and oral cavity and suggest that the protein functions in the complex milieu that protects the mucosal surfaces in these locations.

Chemokine (C-X-C motif) ligand 9 (CXCL9, MIG), is a small cytokine belonging to the CXC chemokine family. CXCL9 functions as one of the three ligands of chemokine receptor CXCR3 which is a G protein-coupled receptor found predominantly on T cells. It together with CXCL10 and CXCL11, may activate CXCR3 by binding to it. CXCL9 serves as a cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory response. It has been observed that tumour endothelial cells secrete high levels of CXCL9 in all, and CXCL10 in most melanoma metastases. it plays an important role in CD4+ T lymphocyte recruitment and development of CAV, MOMA-2+ macrophages are the predominant recipient-derived source of CXCL9, and recipient CD4 lymphocytes are necessary for sustained CXCL9 production and CAV development in this model.

C-C motif chemokine 5(CCL5) is a β-chemokine that plays a primary role in the inflammatory immune response by means of its ability to attract and activate leukocytes. CCL5 is secreted by many cell types at inflammatory sites, and it exerts a wide range of activities through the receptors CCR1, CCR3, CCR4, and CCR5. Inflammatory responses can be impaired by the sequestration of CCL5 by the cytomegalovirus protein US28. Oligomerization of CCL5 on glycosaminoglycans is required for CCR1mediated leukocyte adhesion and activation as well as CCL5’s interaction with the chemokine CXCL4/PF4.The deposition of CCL5 on activated vascular endothelial cells is crucial for monocyte adhesion to damaged vasculature, but CCL5 oligomerization is not required for the extravasation of adherent leukocytes.CCL5 is upregulated in breast cancer and promotes tumor progression through the attraction of proinflammatory macrophages in addition to its actions on tumor cells, stromal cells, and the vasculature.

Tyrosine-protein kinase Mer (MERTK) is a single-pass type I membrane protein which belongs to the MER/AXL/TYRO3 receptor kinase family. MERTK include two fibronectin type-III domains, two Ig-like C2-type domains, and one tyrosine kinase domain. It can’t be expressed in normal B- and T-lymphocytes, but it is usually expressed in numerous neoplastic B- and T-cell lines. MERTK could regulate many physiological processes, such as cell survival, migration, differentiation. It was demonstrated that the MERTK plays critical role in the engulfment and efficient clearance of apoptotic cells, platelet aggregation, and cytoskeleton reorganization. Not only these, it also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response by activating STAT1, which selectively induces production of suppressors of cytokine signaling SOCS1 and SOCS3. In addition, MERTK could regulate rod outer segments fragments phagocytosis in the retinal pigment epithelium (RPE)， deficiency in MERTK are the cause of retinitis pigmentosa.

C-type lectin domain family 2, member D (CLEC2D) is implicated in the immune response. Sensing tissue damage is an ancient function of immune cells that is central to the regulation of inflammation, tissue repair, and immunity. The C-type lectin receptor Clec2d as a sensor of cell death, which directly detects histones released during necrosis and thus contributes to inflammation and immunopathology. The Clec2d pathway may also be exploited to favor a pro-inflammatory anti-tumor response. And tumor cells can show reduced global levels of histone modification, which may favor Clec2d sensing. The contrasting expression of CLEC2D in HIV infection and pre-eclampsia is demonstrative of the immunosuppressive and pro-inflammatory roles of the respective pathologies.