CD152 [CTLA-4] (human) (rec.) (His) Reference: AG-40B-0228 CD152 (Cytotoxic T-lymphocyte-associated protein 4; CTLA-4) is an inhibitory receptor belonging to the CD28 immunoglobulin subfamily, expressed primarily by T-cells. Its ligands, CD80 and CD86, are typically found on the surface of antigen-presenting cells and can either bind CD28 or CTLA-4, resulting in a costimulatory or a co-inhibitory response, respectively. Because of its dampening effect, CTLA-4 is a crucial regulator of T-cell homeostasis and self-tolerance. While CD28 promotes T-cell activation and proliferation, CTLA-4 is reported to dampen T-cell responses through a variety of mechanisms. Prior to activation, conventional T-cells (Tconv) express low levels of CTLA-4, predominantly in intracellular compartments. Upon activation, CTLA-4 expression is upregulated and becomes increasingly detectable on the cell surface. In Tregs on the other hand, transmembrane CTLA-4 is constitutively expressed and plays an important role in Treg homeostasis and function. In general, T-cell CTLA-4 is largely constrained to intracellular expression although some surface expression may be detectable owing to the rapid, continuous shuttling of CTLA-4 between intracellular compartments and the plasma membrane. Recently, roles of CTLA-4 have been demonstrated in dendritic cells and tumors, showing that CTLA-4 plays nonredundant and critical roles in thymic development, T-cell priming, peripheral tolerance, and a variety of other critical immunoregulatory functions as an immune checkpoint in Immuno-oncology research.
Sortilin (human) (rec.) (His) Reference: AG-40B-0229 Sortilin is a type I transmembrane multiligand receptor that is a member of the Vacuolar protein sorting 10 protein (Vps10p) domain receptor family. It is a 95 kDa protein, ubiquitously expressed, although most abundantly expressed in neurons, hepatocytes, adipocytes and white blood cells including macrophages. Sortilin is synthesized as a propeptide in the endoplasmic reticulum (ER) and processed to its mature form by furin-mediated cleavage in the trans-Golgi network. The primary function of sortilin is trafficking proteins from the Golgi to secretory vesicles and endolysosomal compartments. The majority of trafficking is from the Golgi to the endosomal compartment where sortilin deposits cargo targeted for catabolism in the lysosome and then is trafficked back to the Golgi via a retromer complex. At the cell surface, sortilin can remain intact and act as a receptor for extracellular ligands that can initiate signaling cascades or be internalized as a method of receptor-mediated endocytosis. Additionally, cell surface sortilin protein can undergo an additional cleavage that results in the release of the soluble form of the protein into the extracellular space. The sortilin receptor binds the nerve growth factor precursor (proNGF), neurotensin and Progranulin (PGRN), a secreted growth factor implicated in a multitude of processes ranging from regulation of inflammation to wound healing, tumorigenesis and neurological diseases. Sortilin controls PGRN trafficking and lysosomal degradation, but PGRN exerts its multiple functions independent of sortilin. Sortilin down-regulation via blocking antibodies is a key mechanism in increasing PGRN levels suggesting that sortilin is a potential target to correct PGRN reduction, such as that in patients with frontotemporal dementia (FTD) caused by GRN mutations.
IL-22 (human):Fc (human) (rec.) (non-lytic) Reference: AG-40B-0230 The IL-22 gene includes five exons and a 537 bp-long open reading frame that encodes for a 179 amino acid protein. IL-22 is a member of the IL-10 family of cytokines, which also includes IL-19, -20, -24, and -26, IL-28A/B, and IL-29 and IFNlambda. Mouse and human IL-22 share 79% homology. IL-22 is mainly produced by lymphocytes, such as T helper type 1 (Th1), Th17, Th22, CD8+ T cells, gammadelta T cells, natural killer cells, lymphoid tissue inducer cells, innate lymphoid type 3 (ILC3) cells, and also by neutrophils. IL-22 has two heterodimeric transmembrane receptors, IL-22R1 and IL-10R2, which subsequently activate the JAK/STAT3, ERK and JNK pathways. IL-22 responsiveness is limited by epithelial cell-restricted expression of IL-22RA1 in the lung, gastrointestinal tract, thymus, skin, pancreas, liver, and kidney and represents a major communication channel between the immune system and specialized tissue cell types. IL-22 is a critical regulator of epithelial homeostasis, implicated in multiple aspects of epithelial barrier function, including regulation of epithelial cell growth and permeability, production of mucus and antimicrobial proteins (AMPs) and complement production. IL-22 plays key functions in the intestine and, therefore, plays a protective role in inflammatory bowel disease (IBD). IL-22 is also a controversial cytokine in tumor development; the IL-22-STAT3 axis induces anti-apoptotic genes and provides survival and proliferation signals for both normal and malignant cells. Therefore, in healthy conditions, it prevents tumor formation; however, once a tumor has been established, IL-22 promotes tumorigenesis.
CD24 (human)-muIg Fusion Protein Reference: ANC-559-020 CD24 is a highly glycosylated protein expressed as glycosyl-phosphatidyl-inositol (GPI) anchored molecule. It is widely expressed, mainly on T cells, B cells and is upregulated in numerous types of cancers. It has costimulatory activity for antigen specific T cell responses. Polymorphisms of human CD24 are associated with several autoimmune diseases. Recently, a new role as negative regulator of the immune response has been reported. CD24-deficient mice are more sensitive to inflammatory responses. CD24 together with the membrane protein SIGLEC interacts with danger-associated molecular patterns (DAMPs), such as HMGB1, HSP90 or HSP70. CD24/SIGLEC complex may differentially regulate the host response to DAMPs and PAMPs (pathogen-associated molecular patterns).
CD24 (human)-muIg Fusion Protein (preservative free) Reference: ANC-559-820 CD24 is a highly glycosylated protein expressed as glycosyl-phosphatidyl-inositol (GPI) anchored molecule. It is widely expressed, mainly on T cells, B cells and is upregulated in numerous types of cancers. It has costimulatory activity for antigen specific T cell responses. Polymorphisms of human CD24 are associated with several autoimmune diseases. Recently, a new role as negative regulator of the immune response has been reported. CD24-deficient mice are more sensitive to inflammatory responses. CD24 together with the membrane protein SIGLEC interacts with danger-associated molecular patterns (DAMPs), such as HMGB1, HSP90 or HSP70. CD24/SIGLEC complex may differentially regulate the host response to DAMPs and PAMPs (pathogen-associated molecular patterns).
Fc (human) IgG1 Control (rec.) (non-lytic) Reference: AG-35B-0016 Negative control in experiments with recombinant proteins fused to Fc (human) IgG1 (non-lytic) (e.g. Prod. No. AG-40B-0230). This protein is not an appropriate negative control for other standard Fc protein constructs. Mutations to the complement (C1q) and FcgR I binding sites of the IgGs Fc fragment render the non-lytic proteins incapable of antibody-directed cytotoxicity (ADCC) and complement-directed cytotoxicity (CDC).
Fc (mouse) IgG2a Control (rec.) (non-lytic) Reference: AG-35B-0017 Negative control in experiments with recombinant proteins fused to Fc (mouse IgG2a (non-lytic) (e.g. Prod. No. AG-40B-0231). This protein is not an appropriate negative control for other standard Fc protein constructs. Mutations to the complement (C1q) and FcgR I binding sites of the IgGs Fc fragment render the non-lytic proteins incapable of antibody-directed cytotoxicity (ADCC) and complement-directed cytotoxicity (CDC).
IL-22 (mouse):Fc (mouse) (rec.) (non-lytic) Reference: AG-40B-0231 The IL-22 gene includes five exons and a 537 bp-long open reading frame that encodes for a 179 amino acid protein. IL-22 is a member of the IL-10 family of cytokines, which also includes IL-19, -20, -24, and -26, IL-28A/B, and IL-29 and IFNlambda. Mouse and human IL-22 share 79% homology. IL-22 is mainly produced by lymphocytes, such as T helper type 1 (Th1), Th17, Th22, CD8+ T cells, gammadelta T cells, natural killer cells, lymphoid tissue inducer cells, innate lymphoid type 3 (ILC3) cells, and also by neutrophils. IL-22 has two heterodimeric transmembrane receptors, IL-22R1 and IL-10R2, which subsequently activate the JAK/STAT3, ERK and JNK pathways. IL-22 responsiveness is limited by epithelial cell-restricted expression of IL-22RA1 in the lung, gastrointestinal tract, thymus, skin, pancreas, liver, and kidney and represents a major communication channel between the immune system and specialized tissue cell types. IL-22 is a critical regulator of epithelial homeostasis, implicated in multiple aspects of epithelial barrier function, including regulation of epithelial cell growth and permeability, production of mucus and antimicrobial proteins (AMPs) and complement production. IL-22 plays key functions in the intestine and, therefore, plays a protective role in inflammatory bowel disease (IBD). IL-22 is also a controversial cytokine in tumor development; the IL-22-STAT3 axis induces anti-apoptotic genes and provides survival and proliferation signals for both normal and malignant cells. Therefore, in healthy conditions, it prevents tumor formation; however, once a tumor has been established, IL-22 promotes tumorigenesis.
IL-37 (human) (monomeric):Fc-KIH (human) (rec.) Reference: AG-40B-0221 IL-37 (IL-1F7; IL-1H4) is an IL-1 family member that is expressed only in certain types of human organs and cells such as heart, thymus, testis, kidney, mononuclear cells (PBMCs) and dendritic cells. IL-37 is a soluble and secreted cytokine of 218 residues that shares the beta-trefoil fold common to IL-1 family cytokines. But IL-37 is an atypical member of the IL-1 family of cytokines as it functions to inhibit many of the major pathways of innate and adaptive immunity and inflammation. It binds to the interleukin-18 receptor (IL-18R) and its co-receptor SIGIRR. IL-37 is secreted as a full-length and as a processed form starting from amino acid Val46 and assembles into an activity-limiting dimer with a dimerization constant in the nanomolar range. IL-37 mutations that lock the cytokine into its monomeric conformation (e.g. Y85A and D73K) are more active at blocking inflammation than wild-type dimer-forming IL-37 in a broad range of in vitro and in vivo activity assays. IL-37 also inhibited Lipopolysaccharide (LPS)-induced immunological reaction and LPS-induced osteoclast formation and bone resorption. IL-37 (human) (monomeric):Fc-KIH (human) (rec.) (Prod. No. AG-40B-0221) is a new recombinant monomeric IL-37 produced in mammalian cells that has enhanced stability and activity compared to the classical human recombinant IL-37 produced in bacteria. This monomeric IL-37 protein is produced by using two different vectors, one encoding for the IL-37 (monomeric):Fc Knobs sequence (synthesizing a protein of 50kDa) and one encoding for the Fc Holes sequence (synthesizing a protein of 28kDa). Both vectors transfected into HEK293 cells produce both Fc molecules (Knobs-into-Holes technology; J.B. Ridgway, et al.; Protein Eng. 9, 617 (1996)) required for dimerization and for secretion of the final protein IL-37 (human) (monomeric):Fc-KIH (human) (rec.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.
CD152 [CTLA-4] (human) (rec.) (untagged) Reference: AG-40B-0232 CD152 (Cytotoxic T-lymphocyte-associated protein 4; CTLA-4) is an inhibitory receptor belonging to the CD28 immunoglobulin subfamily, expressed primarily by T cells. Its ligands, CD80 and CD86, are typically found on the surface of antigen-presenting cells and can either bind CD28 or CTLA-4, resulting in a costimulatory or a co-inhibitory response, respectively. Because of its dampening effect, CTLA-4 is a crucial regulator of T cell homeostasis and self-tolerance. While CD28 promotes T cell activation and proliferation, CTLA-4 is reported to dampen T cell responses through a variety of mechanisms. Prior to activation, conventional T cells (Tconv) express low levels of CTLA-4, predominantly in intracellular compartments. Upon activation, CTLA-4 expression is upregulated and becomes increasingly detectable on the cell surface. In Tregs on the other hand, transmembrane CTLA-4 is constitutively expressed and plays an important role in Treg homeostasis and function. In general, T cell CTLA-4 is largely constrained to intracellular expression although some surface expression may be detectable owing to the rapid, continuous shuttling of CTLA-4 between intracellular compartments and the plasma membrane. Recently, CTLA-4 has been studied in dendritic cells and tumors, showing that CTLA-4 plays nonredundant and critical roles in thymic development, T cell priming, peripheral tolerance, and a variety of other critical immunoregulatory functions as an immune checkpoint in Immuno-oncology research.
IL-33 (oxidation resistant) (human) (monomeric):Fc-KIH (human) (rec.) Reference: AG-40B-0233 Interleukin-33 (IL-33; HF-NEV; IL-1F11), a member of the IL-1 family of cytokines, is expressed by many cell types following pro-inflammatory stimulation and is thought to be released upon cell lysis. IL-33 binds to and signals through ST2 (IL-1R1) and its stimulation recruits MYD88, IRAK, IRAK4 and TRAF6, followed by phosphorylation of ERK1 (MAPK3) / ERK2 (MAPK1), p38 (MAPK14) and JNK. The ability of IL-33 to target numerous immune cell types, like Th2-like cells, mast cells and B1 cells, and to induce cytokine and chemokine production underlines its potential in influencing the outcome of a wide range of diseases, such as arthritis, asthma, atopic allergy & anaphylaxis, cardiovascular disease/atherosclerosis, nervous system diseases and sepsis. IL-33 facilitates Treg expansion in vitro and in vivo. Recently, IL-33 has been involved in adipocyte differentiation. The biological activity of IL-33 at its receptor ST2 is rapidly terminated in the extracellular environment by its oxidation (formation of two disulfide bridges), resulting in an extensive conformational change that disrupts the ST2 binding site. Mutations at amino acids C208S/C232S protect IL-33 from oxidation and increase its activity. The protein IL-33 (oxidation resistant) (human) (monomeric):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-33 (human) (oxidation resistant):Fc Knobs sequence (synthesizing a protein of 55kDa) and one encoding for the Fc Holes sequence (synthesizing a protein of 28kDa). Both vectors transfected into HEK293 cells produce both Fc molecules (Knobs-into-Holes technology; J.B. Ridgway, et al.; Protein Eng. 9, 617 (1996)) required for dimerization and for secretion of the final protein IL-33 (oxidation resistant) (human) (monomeric):Fc-KIH (human) (rec.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.
IL-2 (human) (Switch-2) (monomeric):Fc-KIH (human) (rec.) Reference: AG-40B-0234 Interleukin-2 (IL-2) is a 133 amino acid glycoprotein with one intramolecular disulfide bond and variable glycosylation. It is secreted by activated T cells and induces proliferation and maturation of activated T cells, natural killer cells and lymphokine activated killer cells. IL-2 also stimulates proliferation of antibody-producing B cells, activates neutrophils and induces mononuclear cells to secrete IFN-gamma and TNF-alpha and -beta. Moreover, studies have shown that IL-2 is required for activation-induced apoptosis, an important homeostatic mechanism in the immune system, which is involved in the maintenance of peripheral tolerance to self-antigens. IL-2 promotes T cell proliferation and particularly naive T cells. IL-2 signaling on activated T cells is effected through a quaternary high-affinity receptor complex consisting of IL-2, IL-2Ralpha (CD25), IL-2Rbeta and IL-2Rgamma. Naive T cells are relatively insensitive to IL-2 as they only express small amounts of IL-2Rbeta and IL-2Rgamma. They only acquire sensitivity after CD25 expression, which captures the cytokine and presents it to the IL-2Rbeta and IL-2Rgamma receptors. Activity of interleukin-2 (IL-2), is profoundly affected by pH, limiting IL-2 signaling within the acidic environment of tumors. A new designed IL-2, named Switch-2, binds the IL-2 receptor subunit IL-2Ralpha with higher affinity, triggers STAT5 activation and drives CD8+ T cell effector function more potently at acidic pH than at neutral pH. The protein IL-2 (human) (Switch-2) (monomeric):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-2 (human) (Switch-2):Fc Knobs sequence (synthesizing a protein of 45kDa) and one encoding for the Fc Holes sequence (synthesizing a protein of 28kDa). Both vectors transfected into HEK293 cells produce both Fc molecules (Knobs-into-Holes technology; J.B. Ridgway, et al.; Protein Eng. 9, 617 (1996)) required for dimerization and for secretion of the final protein IL-2 (human) (Switch-2) (monomeric):Fc-KIH (human) (rec.). InVivoKines™ are a new generation of recombinant fusion proteins for immunotherapeutic, preclinical and translational in vivo research, developed and manufactured by AdipoGen Life Sciences.