GenScript Biotech

The adrenoceptors ADRA2A is expressed in the brain, spleen, kidney, aorta, lung, skeletal muscle, heart and liver. ADRA2A -adrenoceptor knockout mice exhibit disruption of presynaptic inhibition of noradrenaline release at high stimulation frequencies. ADRA2A receptor is the principal autoreceptor in the presynaptic feedback loop regulating noradrenaline release. However, another α2 autoreceptor is also present.

Adrenoceptors are 7-transmembrane receptors which mediate the central and peripheral actions of the neurotransmitter, noradrenaline (norepinephrine), and the hormone and neurotransmitter, adrenaline (epinephrine). Based on both pharmacological and molecular evidence, they are divided into three major types – α1, α2, and β. The α2 adrenoceptors include 3 subtypes – α2A, α2B, and α2C – each of which couples to G_i/o protein primarily.
The α2B adrenoceptors (ADRA2B) is expressed in the kidney, liver, brain, lung, heart, and skeletal muscle. The development of α2B and α2C knock-out mice has shown that these two subtypes are not involved in the central hypotensive response to α2 agonists.

The adrenoceptors ADRA2C is expressed in the brain, kidney, aorta, lung, skeletal muscle, heart and spleen. ADRA2C knockout mice exhibited disrupts presynaptic inhibition of noradrenaline release at low stimulation frequencies.

The ß-adrenergic receptors are linked to G proteins. The ß-receptor has three known subtypes. Beta-1 receptors primarily regulate myocardial tissue and affect the rate of contraction via impulse conduction. Beta-2 receptors regulate smooth muscle tone and influence vascular and bronchiolar relaxation. Beta-3 receptors are less well studied but are thought to primarily affect lypolysis and may have effects on cardiac inotropy (Greene Shepherd，2006). In the human heart, beta (1)- and beta (2)AR are the most powerful physiologic mechanism to acutely increase cardiac performance. Changes in betaAR play an important role in chronic heart failure (CHF). Thus, due to increased sympathetic activity in CHF, betaAR are chronically (over) stimulated, and that results in beta (1) AR desensitization and alterations of down-stream mechanisms (Brodde OE，2006).

The apelin receptor AGTRL1 is G_i/G_o-coupled GPCRs expressed in the heart, coronary artery, aorta, internal mammary artery, pulmonary artery and saphenous vein, it also expressed in lung, kidney and adrenal gland. In AGTRL1 receptor knockout mice baseline blood pressure is not changed compared to wild-type animals. Vasoconstrictor responses to angiotensin II however are significantly more pronounced in the knockout animals.

Bradykinin (BK) is a pro-inflammatory polypeptide that can cause pain, inflammation, increased vascular permeability, vasodilation, contraction of various smooth muscles, and cell proliferation by stimulating B1and B2 receptors. B2 receptors are most commonly distributed in the vascular and non-vascular smooth muscle and in the heart. The B2 receptor mediates the action of bradykinin (BK) and lysyl-bradykinin (Lys-BK). The stimulation of BK B2 receptors is not only implicated in the pathogenesis of inflammation, pain, and tissue injury but also in cardioprotective mechanisms. So B2 receptor agonists may have important clinical value in the treatment and prevention of various cardiovascular disorders such as hypertension, ischaemic heart disease, left ventricular hypertrophy, ventricular remodeling, congestive heart failure, and diabetic disorders.

Ligand for the T-cell-specific cell surface receptor ICOS acts as a costimulatory signal for T-cell proliferation and cytokine secretion. It also induces B-cell proliferation and differentiation into plasma cells. It could also play an important role in mediating local tissue responses to inflammatory conditions, as well as modulating the secondary immune response by co-stimulating memory T-cell function.

B7-H3, a new member of the B7 family of immune-regulatory molecules, was identified in 2001 by database searches of a human dendritic cell-derived cDNA library. It is a type I transmembrane protein, which expresses in certain normal cells and tissues, such as dendritic cells, as well as the liver, lung, breast, placenta, and prostate. Aberrant expression of B7-H3 has been reported in a wide range of solid cancers, including brain, lung, pancreatic, colorectal, liver, and breast cancers, as well as in hematologic malignancies, such as acute leukemia and multiple myeloma, and it is associated with more advanced disease and poor prognosis.

B7-H4 is a transmembrane protein that binds an unknown receptor on activated T cells resulting in inhibition of T-cell effector function via cell cycle arrest, decreased proliferation, and reduced IL-2 production. B7-H4 is up-regulated on the surface of cancer cells and immunosuppressive tumor-associated macrophages (TAMs) in a variety of human cancers.

The bombesin receptor family is a member of the G protein-coupled receptor superfamily and consists of three subtypes of receptors: BB1 (neuromedin B receptor), BB2 (gastrin-releasing peptide receptor), and BB3. These receptors are widely distributed in mammals especially in the CNS and gastrointestinal tract and have numerous effects both physiologically and in pathologic processes including having an autocrine growth action on normal tissues and tumors; potent CNS effects (satiety, circadian rhythm, various behaviors); and potent effects in the immune, gastrointestinal, respiratory and urogenital systems.
The human BB1 receptor has a greater than 100-fold higher affinity for neuromedin B than gastrin-releasing peptide. Interaction of ligand and BB1 activates the G_αq/11 pathway and increase the intracellular calcium concentration. GenScript’s BB1-expressing stable cell line was made in CHO-K1 host cell and optimized for calcium assays.

The bombesin receptor family is a member of the G protein-coupled receptor superfamily and consists of three subtypes of receptors: BB1 (neuromedin B receptor), BB2 (gastrin-releasing peptide receptor), and BB3. These receptors are widely distributed in mammals especially in the CNS and gastrointestinal tract and have numerous effects both physiologically and in pathologic processes including having an autocrine growth action on normal tissues and tumors; potent CNS effects (satiety, circadian rhythm, various behaviors); and potent effects in the immune, gastrointestinal, respiratory and urogenital systems.
The human BB2 receptor has a greater than 50-fold higher affinity for gastrin-releasing peptide than neuromedin B. Interaction of ligand and BB2 activates the G_αq/11 pathway and increase the intracellular calcium concentration. GenScript’s BB2-expressing stable cell line was made in CHO-K1 host cell and optimized for calcium assays.

The bombesin receptor family is a member of the G protein-coupled receptor superfamily and consists of three subtypes of receptors: BB1 (neuromedin B receptor), BB2 (gastrin-releasing peptide receptor), and BB3. These receptors are widely distributed in mammals especially in the CNS and gastrointestinal tract and have numerous effects both physiologically and in pathologic processes including having an autocrine growth action on normal tissues and tumors; potent CNS effects (satiety, circadian rhythm, various behaviors); and potent effects in the immune, gastrointestinal, respiratory and urogenital systems.
BB3 is an orphan receptor, with a high degree of homology to the BB1 and BB2 receptors, but has an unknown natural ligand because it has low affinity for all naturally occurring bombesin-related peptides. Interaction of ligand and BB3 activates the Gαq/11 pathway and increase the intracellular calcium concentration. GenScript’s BB3-expressing stable cell line was made in CHO-K1 host cell and optimized for calcium assays.

BDCA-2 is a novel type II C-type lectin, which shows 50.7% sequence identity at the amino acid level to its putative murine ortholog, the murine dendritic cell–associated C-type lectin 2. In addition to its antigen capturing function, BDCA-2 can mediate potent inhibition of induction of IFN-α/β expression in PDCs. Production of IFN-α/β in response to several different types of viruses, bacteria, CpG-DNA, dsRNA, and SLE serum is by far the most prominent feature of PDCs.

BDCA-2 is a novel type II C-type lectin, which shows 50.7% sequence identity at the amino acid level to its putative murine ortholog, the murine dendritic cell–associated C-type lectin 2. In addition to its antigen capturing function, BDCA-2 can mediate potent inhibition of induction of IFN-α/β expression in PDCs. Production of IFN-α/β in response to several different types of viruses, bacteria, CpG-DNA, dsRNA, and SLE serum is by far the most prominent feature of PDCs.

The B and T lymphocyte attenuator (BTLA) is an Ig super family protein with an intermediate type Ig fold in the ectodomain and an ITIM inhibitory signaling domain in the cytosol. BTLA interacts with the herpesvirus entry mediator (HVEM; TNFRSF14), a TNFR super family member. Engagement of BTLA by HVEM, induces tyrosine phosphorylation of the ITIM motifs in the cytoplasmic tail of BTLA, allowing the recruitment of the phosphatases SHP-1 and SHP-2, which attenuate signaling.

The complement component 5a receptor 1 (C5a) is G_q/11 and G_i/o-coupled GPCRs. C5a is a significant pathogenic driver in a number of immuno-inflammatory diseases, making C5a inhibition an attractive therapeutic strategy. C5a receptor plays an important role in mediating acute kidney allograft rejection.

CASR is a calcium-sensing receptor and plays an important role in regulating PTH secretion. It is expressed in many different tissues, such as parathyroid, pancreatic islet and insulinoma cells, breast, gastrinoma cells, pituitary, keratinocytes and human colon epithelial cells. CASR Inhibits PTH secretion and parathyroid cellular proliferation in parathyroid glands or cells, and also inhibits proliferation of colonic crypt cells. Besides, it can stimulate PTHrP secretion in prostate cell line, and stimulate calcitonin secretion from thyroidal C-cells.

The cannabinoid receptor CNR1 is Gs-coupled GPCRs expressed in primarily CNS and some peripheral neurones; particularly prevalent in basal ganglia, hippocampus, cerebellum, cerebral cortex and also presented in some non-neuronal cells and tissues, for example leukocytes and testis. A shorter human splice variant (411aa) has been identified in the brain and other tissues by reverse-transcriptase PCR but mRNA levels were less than 10-fold the levels of the longer isoform. The pharmacological characteristics of the isoforms are similar.

The Cannabinoid receptor 2 (CNR2) is a G_i/o-coupled GPCR expressed in spleen, tonsils, bone marrow and peripheral blood leukocytes. There is one report that cannabinoid-induced inhibition of helper T cell activation is lost in macrophages obtained from CNR2 knockout mice. CNR2 is a potential therapeutic target in the treatment of various disease conditions, such as pain, multiple sclerosis, vascular disease, Parkinson’s disease, and other central nerve system disorders.

Cholecystokinin (CCK)-A and CCK-B receptors are highly homologous members of the seven transmembrane domain G-protein-coupled receptor super-family. Peptides in the cholecystokinin (CCK) family have a variety of biological functions in the central and peripheral nervous systems as well as in the gastrointestinal tract. The CCKA receptor has a more limited distribution with the highest densities in the hypothalamic nuclei, areas of the hippocampus, the septum, dorsal motor vagal nucleus, and interpeduncular nucleus of the brain stem. It also occurs in numerous gastro-intestinal tissues. Binding of ligands to CCK1 stimulates mobilization of intracellular calcium by activation of Gq/11. CCKA receptors affect satiety, pancreatitis, and gut motility and have growth-promoting effects on some tumors.

Cholecystokinins (CCK) are derived from preprocholecystokinin. They are widely expressed in gastrointestinal tissues and in the CNS. There are two cholecystokinin receptors, referred to as A and B (CCKAR and CCKBR). CCKBR can be activated by the smaller CCK-4 (7, 8). In the CNS, CCKBR has been implicated in anxiety, depression, schizophrenia, depression, and opioid analgesia. In the stomach, CCK2 mediates gastrin-stimulated gastric acid secretion.

Cluster of Differentiation 112 (CD112), also known as poliovirus receptor related protein 2 (PVRL2 or PRR2), is a single-pass type I transmembrane glycoprotein belonging to the Immunoglobulin superfamily. CD112 protein also serves as an entry for certain mutant strains of herpes simplex virus and pseudorabies virus, and thus is involved in cell to cell spreading of these viruses. CD112 protein has been identified as the ligand for DNAM-1 (CD226), and the interaction of CD226/CD112 protein can induce NK cell- and CD8+ T cell-mediated cytotoxicity and cytokine secretion. CD112 has been regarded as a critical component in allergic reactions, and accordingly may function as a novel target for anti-allergic therapy.

CD155, commonly known as PVR (poliovirus receptor) and Necl-5 (nectin-like molecule-5), is a type I transmembrane single-span glycoprotein, and belongs to the nectins and nectin-like (Necl) subfamily. CD155 was originally identified based on its ability to mediate the cell attachment and entry of poliovirus (PV), an etiologic agent of the central nervous system disease poliomyelitis. The normal cellular function is in the establishment of intercellular adherens junctions between epithelial cells. CD155 may assist in an efficient humoral immune response generated within the intestinal immune system. It’s been shown that CD155 can be recognized and bind by DNAM-1 and CD96, which promotes the adhension, migration and NK-cell killing. Thus, inducing cell-mediated tumor-specific immunity.

Recombinant CHO-K1 cells stably overexpress low affinity immunoglobulin gamma Fc region receptor III-A (FcγRIIIa / CD16A 158F) complex on the cell surface, including 1 alpha chain and 2 gamma chains. The surface expression of CD16A is validated by FACS analysis. This stable cell line product is designed for measuring binding affinity and stability of the Fc region of antibodies, Fc fusion proteins, or antibody based biologics that bind with CD16A 158F. GenScript also offers a stable cell line expressing the CD16A of 158V allotype (Cat. No. M00597) for FcγRIIIa polymorphism study.

Recombinant CHO-K1 cells stably express low affinity immunoglobulin gamma Fc region receptor III-A (FcγRIIIa / CD16A 158V) complex on the cell surface, including 1 alpha chain and 2 gamma chains. The surface expression of CD16A is validated by FACS analysis. This stable cell line product is designed for measuring the binding affinity and stability of the Fc region of antibodies, Fc fusion proteins, or antibody based biologics that bind with CD16A 158V. GenScript also offers a stable cell line expressing the CD16A of 158F allotype (Cat. No. M00598) for FcγRIIIa polymorphism study.

Recombinant CHO-K1 cells stably overexpress human Fc fragment of IgG receptor IIIb (FcγRIIIb / CD16B NA1). The surface expression of CD16B NA1 is validated by FACS analysis. This stable cell line product is designed for measuring binding affinity and stability of Fc region of antibodies, Fc fusion proteins, or antibody based biologics that bind with CD16B during biologics research and development.

Cell surface glycoprotein CD200 receptor 1 is a protein that in humans is encoded by the CD200R1 gene. This gene encodes a receptor for the OX-2 membrane glycoprotein. Both the receptor and substrate are cell surface glycoproteins containing two immunoglobulin-like domains. This receptor is restricted to the surfaces of myeloid lineage cells and the receptor-substrate interaction may function as a myeloid downregulatory signal. Mouse studies of a related gene suggest that this interaction may control myeloid function in a tissue-specific manner.

Recombinant CHO-K1 cells stably overexpress immunoglobulin gamma Fc region receptor II-a (FcγRIIa / CD32A 131Arg). The surface expression of CD32A 131Arg is validated by FACS analysis. This stable cell line product is designed for measuring binding affinity and stability of antibody based biologics binding with CD32A 131Arg. GenScript offers both CD32A 131Arg stable cell line and CD32A 131His stable cell line (Cat. No. M00589) for FcγRIIa polymorphism study.

Recombinant CHO-K1 cells stably overexpress low affinity immunoglobulin gamma Fc region receptor II-b (FcγRIIb / CD32B 232Thr). The surface expression of CD32B 232Thr is validated by FACS analysis. This stable cell line product is designed for measuring binding affinity and stability of Fc region of antibodies, Fc fusion proteins, or antibody based biologics that bind with CD32B 232Ile. GenScript also offers CD32B 232Ile overexpression stable cell line (Cat. No. M00587) for FcγRIIb polymorphism study.

Recombinant CHO-K1 cells stably overexpress low affinity immunoglobulin gamma Fc region receptor II-b (FcγRIIb / CD32B 232Ile). The surface expression of CD32B 232Ile is validated by FACS analysis. This stable cell line product is designed for measuring binding affinity and stability of antibody based biologics binding with CD32B 232Ile. GenScript offers both CD32B 232Ile expressing stable cell line and CD32B 232Thr expressing stable cell line (Cat. No. M00600) for FcγRIIb polymorphism study.

Recombinant CHO-K1 cells stably overexpress Homo sapiens cell-type natural killer cells Fc gamma receptor IIc1 (FcγRIIc / CD32C) on the cell surface. The surface expression of FcγRIIc is validated by FACS analysis. This stable cell line is recommended for evaluating the binding affinity between FcγRIIc and Fc region of antibodies, Fc fusion proteins, or antibody-based biologics.

CD38 (cluster of differentiation 38), also known as cyclic ADP ribose hydrolase is a glycoprotein found on the surface of many immune cells (white blood cells), including CD⁴⁺, CD⁸⁺, B lymphocytes and natural killer cells. CD38 also functions in cell adhesion, signal transduction and calcium signaling. In humans, the CD38 protein is encoded by the CD38 gene which is located on chromosome 4. CD38 is a multifunctional ectoenzyme that catalyzes the synthesis and hydrolysis of cyclic ADP-ribose (cADPR) from NAD⁺to ADP-ribose. These reaction products are essential for the regulation of intracellular Ca²⁺.

Recombinant CHO-K1 cells stably overexpress high affinity human Fc fragment of IgG receptor Ia (FcγRI, CD64) on the cell surface, containing one alpha chain and two gamma chains. The surface expression of CD64 is validated by FACS analysis. This stable cell line product is designed for measuring the binding affinity and stability of the Fc region of antibodies, Fc fusion proteins, or antibody based biologics that bind with CD64 during biologics research and development.

Cluster of Differentiation 80 (also CD80 and B7-1) is a protein found on activated B cells and monocytes that provides a costimulatory signal necessary for T cell activation and survival. It is the ligand for two different proteins on the T cell surface: CD28 (for autoregulation and intercellular association) and CTLA-4 (for attenuation of regulation and cellular disassociation). CD80 works in tandem with CD86 to prime T cells.

Claudins are a family of proteins, which play a role in maintaining tight cell junctions. Differentclaudin subtypes are expressed on different tissues.Claudin 18 isoform 2 (CLDN18.2) expressionin normal tissues is restricted to cells of the gastric mucosa and is absent from other healthytissues However, CLDN 18.2 is expressed in 70% of primary gastric adenocarcinomas and itsmetastases (101). It has also been shown to be expressed in a number of other cancers,including pancreatic (50%), esophagus (30%) and NSCLC (25%)The restricted expressionmakes it a potential drug target for the treatment of gastric and pancreatic adenocarcinoma, asevidenced by efforts to target CLDN18.2 via naked antibody and CAR-T modalities.

* The mycoplasma test was
performed with MycoAlert™ PLUS Mycoplasma Detection Kit of Lonza.

The orphan receptor ChemR23 (also referred to as CMKLR1 or DEZ) is a G-protein coupled receptor (GPCR) with homology to neuropeptide and chemoattractant receptors. ChemR23 is also a Gαi-linked receptor expressed primarily by monocytes, MΦs, and plasmacytoid dendritic cells. CMKLR1 has been shown to be expressed by DC generated in vitro from monocytes, to mediate their migration to the proteolytically regulated chemoattractant chemerin, and CMKLR1 may be a key mediator of pDC recruitment from the blood into tissue sites enriched in active chemerin.

This is a cell model with luciferase reporter gene for cell-based assay. CHO-K1/CRE-CBLuc/GLP1R Stable cell line is designed for In Vitro assay to detect the bioactivity of GLP-1 analogue. The binding affininity or the relative potency of the candidate drug can also be evaluated with this cell model.

The CRF1 receptor is a Gs-coupled GPCR expressed in the brain and pituitary gland that binds to several neuropeptides, including corticotropin-releasing factor (CRF) and urocortin, and the amphibian peptide sauvagine. CRF plays a predominant role in stress response mediated by the hypothalamic-pituitary-adrenal axis, and alterations in CRF and its receptors CRF1 and CRF2 appear to be linked to depression and anxiety. In comparison to the CRF2 receptor, the CRF1 receptor has received considerable attention as a potential therapeutic target for the treatment of stress-related disorders such as adrenocorticotropin hypersecretion, increased colonic motility and exaggerated fear and anxiety-related behavior.

The corticotropin-releasing factor receptor 2 CRF2 is Gs-coupled GPCRs expressed in the brain, blood vessels and intestine that bind to corticotropin-releasing factor (CRF). The CRF is a 41-amino acid peptide that plays an important role in the integration of autonomic, neuroendocrine, and behavioral responses to stress. GenScript’s cloned human CRF2-expressing cell line co-expressing Gα15 is made in the CHO-K1 host.

Numerous studies have demonstrated that the calcitonin receptor (CALCR) is a specific marker of osteoclast differentiation and that calcitonin can inhibit bone resorption in vitro and in vivo. Mice lacking calcitonin and calcitonin gene-related peptide (CGRP) have a high bone mass phenotype due to an increase in bone formation parameters. Expression of calcitonin (CT) and its receptor (CTR) generate survival, adhesion, pro-inflammatory, and pro-metastatic pathways. Moreover, data indicate a pivotal role for CT-CTR axis in advanced prostate cancer PC metastasis and may serve as a potential therapeutic target for advanced PC.

CTLA4 or CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152 (cluster of differentiation 152), is a protein receptor that functions as an immune checkpoint and downregulates immune responses. CTLA4 is constitutively expressed in regulatory T cells but only upregulated in conventional T cells after activation – a phenomenon which is particularly notable in cancers. It acts as an “off” switch when bound to CD80 or CD86 on the surface of antigen-presenting cells.

The CTLA-4 protein is encoded by the Ctla4 gene in mice and the CTLA4 gene in humans.

CXCR4 is a receptor for the C-X-C chemokine SDF-1 (Stromal Cell-Derived Factor 1). It is involved in haematopoiesis and cardiac ventricular septum formation, and plays an essential role in vascularization of the gastrointestinal tract, cerebellar development and survival of hippocampal-neuron of central nerve system. CXCR4 also acts as a primary receptor for some HIV-2 isolates and as a co-receptor with CD4 for HIV-1 X4 viruses.

4-1BB is a member of the tumor necrosis factor (TNF) receptor family. Its alternative names are tumor necrosis factor receptor superfamily member 9 (TNFRSF9), CD137 and induced by lymphocyte activation (ILA). It is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule. 4-1BB can be expressed by activated T cells, but to a larger extent on CD8 than on CD4 T cells. In addition, 4-1BB expression is found on dendritic cells, follicular dendritic cells, natural killer cells, granulocytes and cells of blood vessel walls at sites of inflammation.

BDCA-2 is a novel type II C-type lectin, which shows 50.7% sequence identity at the amino acid level to its putative murine ortholog, the murine dendritic cell–associated C-type lectin 2. In addition to its antigen capturing function, BDCA-2 can mediate potent inhibition of induction of IFN-α/β expression in PDCs. Production of IFN-α/β in response to several different types of viruses, bacteria, CpG-DNA, dsRNA, and SLE serum is by far the most prominent feature of PDCs.

BDCA-2 is a novel type II C-type lectin, which shows 50.7% sequence identity at the amino acid level to its putative murine ortholog, the murine dendritic cell–associated C-type lectin 2. In addition to its antigen capturing function, BDCA-2 can mediate potent inhibition of induction of IFN-α/β expression in PDCs. Production of IFN-α/β in response to several different types of viruses, bacteria, CpG-DNA, dsRNA, and SLE serum is by far the most prominent feature of PDCs.

CD155, commonly known as PVR (poliovirus receptor) and Necl-5 (nectin-like molecule-5), is a type I transmembrane single-span glycoprotein and belongs to the nectins and nectin-like (Necl) subfamily. CD155 was originally identified based on its ability to mediate the cell attachment and entry of poliovirus (PV), an etiologic agent of the central nervous system disease poliomyelitis. The normal cellular function is in the establishment of intercellular adherens junctions between epithelial cells. CD155 may assist in an efficient humoral immune response generated within the intestinal immune system. It’s been shown that CD155 can be recognized and bind by DNAM-1 and CD96, which promotes the adhension, migration, and NK-cell killing. Thus, inducing cell-mediated tumor-specific immunity.

This gene encodes a membrane protein, which is involved in the increase in intracellular calcium concentration that occurs upon cell adhesion to extracellular matrix. The encoded protein is also a receptor for the C-terminal cell binding domain of thrombospondin, and it may play a role in membrane transport and signal transduction. This gene has broad tissue, distribution, and is reduced in expression on Rh erythrocytes. Alternatively spliced transcript variants have been found for this gene.

CTLA4 or CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152 (cluster of differentiation 152), is a protein receptor that, functioning as an immune checkpoint, downregulates immune responses. CTLA4 is constitutively expressed in Tregs but only upregulated in conventional T cells after activation. It acts as an

HVEM is found on the surface of various cell types, including hematopoietic and non-hematopoietic cells, and is expressed mainly in spleen, thymus, bone marrow, lung and intestines. It has been identified as a canonical TNF receptor, signaling through the TNF receptor-associated factors (TRAFs) leading to NFκB activation. Furthermore, in addition to acting as a signaling receptor, in binding to Ig superfamily members it acts as a ligand for these inhibitory receptors. Therefore, bidirectional signaling is possible for the HVEM-mediated signaling network, which can be involved in positive or negative immunological reactions under different contexts.

Programmed cell death protein 1, also known as PD-1 and CD279 (cluster of differentiation 279), is a protein that in humans is encoded by the PDCD1 gene. PD-1, functioning as an immune checkpoint, plays an important role in down regulating the immune system by preventing the activation of T-cells, which in turn reduces autoimmunity and promotes self-tolerance. The inhibitory effect of PD-1 is accomplished through a dual mechanism of promoting apoptosis (programmed cell death) in antigen specific T-cells in lymph nodes while simultaneously reducing apoptosis in regulatory T cells (suppressor T cells).