Category: Proteins & Peptides

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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).

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).

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).

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.

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.

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.

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.

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.

Reference: AG-40B-0235

Interleukin-12 (IL-12) family members are heterodimer glycoproteins, composed of two covalently linked subunits, alpha and beta chains. The alpha-subunit consists of IL-23p19, IL-27p28, and IL-12p35, and the beta-subunit includes IL-12p40 and Epstein-Barr virus-induced gene (Ebi3). IL-12 members bind to cognate heterodimeric receptor chains expressed on T cells. This family includes IL-12, IL-23, IL-27, IL-35 and IL-39. IL-12 and IL-23 are predominantly proinflammatory cytokines that contribute key roles in the development of Th1 and Th17 cells, respectively. IL-27 has both pro- and anti-inflammatory properties and is a potent T cell immunomodulator. IL-35, a new member of this family, is a potent inhibitory cytokine produced by natural, thymus-derived regulatory T cell (nTreg) populations. IL-39, the newest member of the IL-12 family, mediates the inflammatory response through the activation of STAT1/STAT3 signaling pathway. These IL-12 family members link innate immunity with the development of adaptive immunity and are also important for regulating T cell responses. Interleukin-23 (IL-23) is composed of the IL-12 p40 chain covalently linked to p19, a chain related to the IL-12 p35 subunit. IL-23 signals through the IL-23 receptor complex, which is composed of the IL-12Rbeta1 chain and a gp130-like chain, IL-23R. Triggering of the IL-23 receptor complex leads to the activation of Tyk2, Jak2 and STAT1, 3 and 4. IL-23 induces IFN-gamma production, Th1 cell differentiation and activation of the antigen-presenting functions of dendritic cells. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and important for tumorigenesis. The protein IL-23 (mouse):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-23A/p19:Fc Knobs sequence (synthesizing a protein of 55kDa) and one encoding for the IL-12B/p40:Fc Holes sequence (synthesizing a protein of 75kDa). Both vectors transfected into CHO 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-23 (mouse): 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.

Reference: AG-40B-0236

Interleukin-12 (IL-12) family members are heterodimer glycoproteins, composed of two covalently linked subunits, alpha and beta chains. The alpha-subunit consists of IL-23p19, IL-27p28, and IL-12p35, and the beta-subunit includes IL-12p40 and Epstein-Barr virus-induced gene (Ebi3). IL-12 members bind to cognate heterodimeric receptor chains expressed on T cells. This family includes IL-12, IL-23, IL-27 and IL-35 and IL-39. IL-12 and IL-23 are predominantly proinflammatory cytokines that contribute key roles in the development of Th1 and Th17 cells, respectively. IL-27 has both pro- and anti-inflammatory properties and is a potent T cell immunomodulator. IL-35, a new member of this family, is a potent inhibitory cytokine produced by natural, thymus-derived regulatory T cell (nTreg) populations. IL-39, the newest member of IL-12 family, mediates the inflammatory response through the activation of STAT1/STAT3 signaling pathway. These IL-12 family members link innate immunity with the development of adaptive immunity and are also important for regulating T cell responses. IL-27 is composed of two subunits, IL-27p28 and Epstein-Barr virus-induced gene 3 (EBI3) signals via a heterodimeric receptor consisting of WSX-1 and glycoprotein (gp130), leading to activation of STAT 1 and 3. IL-27 is pro-inflammatory and promotes NK and T cell proliferation as well as the production of IFN-gamma. It is anti-inflammatory, inhibiting Th2 and Th17 cell activities and stimulating the production of IL-10 by T regulatory cells. IL-27 has potent antiviral activities against numerous viruses, by increasing the production of interferons (IFNs). Finally, IL-27 has antitumor activity as well as anti-angiogenic activity with activation of the production of anti-angiogenic chemokines. The protein IL-27 (mouse):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-27A/p28:Fc Knobs sequence (synthesizing a protein of 62kDa) and one encoding for the IL27B/EBI3: Fc Holes sequence (synthesizing a protein of 60kDa). Both vectors transfected into CHO 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-27 (mouse): 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.

Reference: AG-40B-0237

The V-set and transmembrane domain-containing protein (VSTM) family is composed of 8 proteins: VSTM1v1, VSTM1v2, VSTM2a, VSTM2b, VSTM2L, VSTM3, VSTM4 and VSTM 5. Members of the VSTM family are associated with the regulation of functions of immune cells, adipose cells and neuronal cells. The VSTM family is an immunoglobulin (Ig) superfamily that shares structural similarities with the B7-like transmembrane proteins involved in immune regulation. VSTM1 and VSTM4 play positive and negative roles in macrophage activation, respectively. VSTM3 (TIGIT) acts as a co-inhibitory receptor that suppresses the cytokine production of T cells and NK cells. V-set and transmembrane domain-containing protein 5 (Vstm5), a newly characterized small membrane glycoprotein highly expressed in the CNS, facilitates the formation of neuronal dendrites and protrusions such as dendritic filopodia. Regulatory roles of VSTM5 for in vitro and in vivo immune responses have been reported. VSTM5 functions as a novel immune checkpoint by regulating T cell proliferation and cytokine production, Treg generation by maintenance of T cell energy and possibly induction of T cell apoptosis.

Reference: AG-40B-0238

Interleukin-7 (IL-7) is a hematopoietic growth factor and a member of the IL-7/IL-9 family, which is produced by fetal liver cells, stromal cells in the bone marrow (BM), thymus and other epithelial cells, including keratinocytes and enterocytes. The receptor of IL-7, IL-7R, is a heterodimeric complex consisting of the alpha-chain (CD127) and the common cytokine receptor gamma-chain, shared with the receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21, and expressed in a variety of cells. IL-7 has a critical developmental function at every stage of T cell development, for both alphabeta and gammadelta lineages, and for the development and survival of naive T cells as well as generation and maintenance of CD4 and CD8 memory. IL-7 is also essential for the development and maintenance of the new ILCs. IL-7 is important throughout hematopoiesis, facilitating key lineage fate decisions. IL-7 is thought to support aberrant immune activity in autoimmune diseases such as diabetes and multiple sclerosis and in chronic inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis and inflammatory bowel disease. IL-7 contributes to leukemia development in vivo and also stimulates multiple immune-mediated mechanisms that contribute to the eradication of tumors. The protein IL-7 (human) (monomeric):Fc-KIH (human) (rec.) is produced by using two different vectors, one encoding for the IL-7 (human):Fc Knobs sequence (synthesizing a protein of 60kDa) 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 of the Fc moieties and for secretion of the final protein IL-7 (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.