Targets Associated to Immuno Cell Types - T cells
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The T cells category includes the following Cell Ontology parent terms: |
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Targets Associated to Immuno Cell Types
Full documentation can be found in the GtoImmuPdb immuno cell type data documentation (PDF). ✖ | Download as CSV | ||
| GPCRs | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| S1P1 receptor (Lysophospholipid (S1P) receptors) |
B- and T-lymphocytes predominantly express S1P1 receptors. |
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S1P1R activation by agonists downregulates allergic inflammation (i.e. it has an inhibitory effect) [118,120,229] ... |
| A2B receptor (Adenosine receptors) |
An anti-A2B receptor antibody shows expression in CD4+ and CD8+ T-cell subpopulations. More than 95% of Jurkat T cells were shown to be A2B receptor positive. A2B receptor is expressed by mouse iNKT cells. |
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A2B receptor is discussed in this immuno-oncology review [2] ... |
| β2-adrenoceptor (Adrenoceptors) |
Activation of β2-ARs enhances retention-promoting signals through CCR7 and CXCR4 and inhibits lymphocyte (T cells and other lymphocyte lineages) egress from lymph nodes. In models of T cell-mediated inflammatory diseases, β2-AR-mediated signals inhibit lymph node egress of antigen-primed T cells and reduce their recruitment into peripheral tissues [191].CD8+ T cells (CL:0000625): CD8+ T cells from patients with rheumatoid arthritis express lower levels of β2-ARs compared with healthy subjects [19]. Treg cells (CL:0000815): β2-AR agonist increases Treg-cell suppressive function associated with decreased IL-2 mRNA levels in responder CD4+ T cells and improved Treg-cell-induced conversion of CD4+ Foxp3- cells into Foxp3+ induced Treg cells [99]. |
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β2-ARs are expressed on innate and adaptive immune cells of humans and rodents, and are reported to have an immuno-modulating effect [81] ... |
| CCR3 (Chemokine receptors) |
CCR3 is expressed on mast cells, basophils, and Th2 lymphocytes. |
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CCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. |
| FFA3 receptor (Free fatty acid receptors) |
FFA3 has been included in GtoImmuPdb as its expression has been detected in immune cells [39] ... | ||
| GPR15 (Class A Orphans) |
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Several lines of evidence suggest that GPR15 is a chemoattractant receptor supporting the trafficking of T effector cells to the colon [102,194,197,258] ... | |
| NK1 receptor (Tachykinin receptors) |
T helper cells | Expression in monocytes, macrophages and T helper cells suggests a role in inflammation/immunity. | |
| 5-HT2A receptor (5-Hydroxytryptamine receptors) |
Involved in T cell proliferation. | The chemoattractant properties of 5-HT on human eosinophils is mediated by 5-HT2A receptor [34] ... | |
| 5-HT7 receptor (5-Hydroxytryptamine receptors) |
Involved in T cell proliferation. | 5-HT has been shown to alter cytokine production by dendritic cells via 5-HT4 and 5-HT7 receptors [5] ... | |
| 5-HT1B receptor (5-Hydroxytryptamine receptors) |
Involved in T cell proliferation. | The expression of 5-HT1B receptors on immune cells indicates that it plays some part in immune/inflammatory responses [280] ... | |
| 5-HT1A receptor (5-Hydroxytryptamine receptors) |
The chemoattractant properties of 5-HT on both human and mouse mast cells are mediated by 5-HT1A receptor [146] ... | ||
| CXCR3 (Chemokine receptors) |
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CXCR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR3 is the receptor for CXCL9, -10 and -11, three CXC chemokines that are preferentially expressed on Th1 lymphocytes. In the cancer setting cytokines are known to establish an immunosuppressive milieu that is condusive to tumour progression. CXCR3 and its ligands have specifically been identified as being associated with this mechanism in pancreatic ductal adenocarcinoma [46] ... |
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| A2A receptor (Adenosine receptors) |
A2A receptor is expressed by mouse iNKT cells. Interleukin-4 production is inhibited by A2A receptor blockade in mouse and human iNKT cells. The A2A receptor is required for the secretion of IL-4 and IL-10 by iNKT cells. |
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Agonist stimulation of the A2A and A3 receptors down-regulates production of the pro-inflammatory mediators TNF-α and IL-8 in human synoviocytes [272] ... |
| A1 receptor (Adenosine receptors) |
A1 receptor is expressed by mouse iNKT cells. |
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Adenosine exerts anti-inflammatory effects on a number of immune cells types. These effects are mediated by the adenosine G portein-coupled receptors. All four adenosine receptors are expressed on the surface of mouse invariant NKT (iNKT) cells. The specific role of the A1 receptor in ade ... |
| A3 receptor (Adenosine receptors) |
A3 receptor is expressed by mouse iNKT cells. |
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Agonist stimulation of the A2A and A3 receptors down-regulates production of the pro-inflammatory mediators TNF-α and IL-8 in human synoviocytes [272] ... |
| kisspeptin receptor (Kisspeptin receptor) |
Expressed by thymic and splenic CD4+ T cells, and thymic stromal cells. Highest expression was identified in CD4/CD8 double positive immature thymocytes. |
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Xing et al. (2018) report on the role of the kisspeptin receptor in immune system regulation [297] ... |
| 5-HT2C receptor (5-Hydroxytryptamine receptors) |
Expressed by T cells. | The expression of 5-HT2B receptors on immune cells indicates that it plays some part in immune/inflammatory responses [280] ... | |
| CCR4 (Chemokine receptors) |
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CCR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. In disease states CCR4 is involved in recruiting T helper type 2 cell (Th2) subsets in autoimmune disorders such as asthma, allergic rhinitis, and atopic dermatitis [243] ... |
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| DP2 receptor (Prostanoid receptors) |
Expression of the DP2 receptor is restricted to eosinophils, basophils, Th2 cells, and innate lymphoid cells. |
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The DP2 receptor (a.k.a. CRTH2, chemoattractant receptor-homologous molecule expressed on T-helper 2 cells) is expressed exclusively by a range of human immune cells including Th2 cells, basophils, eosinophils and innate lymphoid cells [109,189] ... |
| GPR55 (GPR18, GPR55 and GPR119) |
GPR55 expression was detected in human immune cells by single cell RNA-sequencing, with expression being highest in CD4+ T cells. |
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| CB2 receptor (Cannabinoid receptors) |
CB2 receptor expression was detected in human CD8+ T cells by single cell RNA-sequencing. Expression was lowest in CD4+ T cells by this method. |
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CB2 receptor on eosinophils mainly mediates anti-inflammatory and immunomodulatory actions e.g. downregulation of pro-inflammatory mediator release. Pharmacological targeting with the CB2 receptor selective antagonist SR144528 attenuates the recruitment of eosinophils and ear swelling in a murine chronic contact dermatitis model [198] ... |
| S1P4 receptor (Lysophospholipid (S1P) receptors) |
Affects Th17 differentiation. |
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| ADGRG1 (Adhesion Class GPCRs) |
ADGRG1 is expressed by CD8+, CD4+ and γδ T cells. |
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An association between ADGRG1 and the tetraspanin CD81, negatively regulates the immediate effector functions (inflammatory cytokine and cytolytic protein production, degranulation, target cell killing) of mature NK cells [55] ... |
| Ion Channels | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| TRPC3 (Transient Receptor Potential channels (TRP)) |
TRPC channels (e.g. TRPC3, TRPC5, TRPC6) are involved in TCR signalling, proliferation and autoimmune suppression. | Expressed on B cells, T cells, neutrophils and monocytes/macrophages [205] ... | |
| TRPC5 (Transient Receptor Potential channels (TRP)) |
TRPC5 (along with TRPC3 and TRPC6) is involved in TCR signalling, proliferation and autoimmune suppression. | Expressed on mouse T cells [205] ... | |
| Kv1.3 (Voltage-gated potassium channels (Kv)) |
Kv1.3 blockade causes inhibition of T cell proliferation and cytokine secretion, particularly in CCR7-effector memory T cells. | Kv1.3 is involved in T cell proliferation, activation and cytokine secretion, most significantly in effector memory T lymphocytes (TEM cells) compared to naive and central memory T cells. TEM cells are major drivers of inflammation in a number of autoimmune diseases, including multiple sclerosis and rheumatoid arthritis, so pharmacological manipulation of Kv1.3 activity may be of clinical utility in immunomodulation [1,24,54,95] ... | |
| KCa3.1 (Calcium- and sodium-activated potassium channels (KCa, KNa)) |
KCa3.1 is expressed in CCR7+ naïve and central memory T cells. It is involved in the activation of, and cytokine production by Th1, Th2 and central memory T cells. | KCa3.1 and KV1.3 are the predominant potassium channels involved in regulating the hyperpolarized (negative) membrane potential which is critical for immune cell activation [75,87,175] ... | |
| Orai1 (Orai channels) |
The Orai1 gene is expressed by a variety of T cell subtypes, some of which are specified here. |
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ORAI1 is the gene that encodes the essential pore-forming subunit of CRAC store-operated Ca2+ entry (SOCE) channels [212] ... |
| Orai2 (Orai channels) |
Orai2 (along with Orai1) is involved in T cell -mediated immune responses (demonstrated in mice in vivo). | The ORAI1 and ORAI2 proteins form heteromeric complexes that constitute the pore of Ca2+ release-activated Ca2+ (CRAC) channels. CRAC channels mediate store-operated Ca2+ entry (SOCE), a function that is essential for proper T cell function. Evidence indicates that ORAI2 fine-tunes SOCE to modulate the immune response [268] ... | |
| TRPM2 (Transient Receptor Potential channels (TRP)) |
TRPM2 activity is involved in T cell activation and cytokine production. | Expressed on human T cells, mouse dendritic cells, human and mouse neutrophils and monocytes/macrophages, and mouse mast cells [205] ... | |
| TRPV1 (Transient Receptor Potential channels (TRP)) |
T cell-expressed TRPV1 regulates the activation and proinflammatory properties of CD4+ T cells. | Several lines of evidence suggest that TRPV1 is implicated in some inflammatory processes [15,30,170,172,226] ... | |
| Cav1.2 (Voltage-gated calcium channels (CaV)) |
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Cav1.2 is implicated in Th2 cell function in asthma [222,267] ... | |
| Cav1.3 (Voltage-gated calcium channels (CaV)) |
Cav1.3 and Cav1.4 are involved in CD8+ T cell survival and cytokine production [201] ... | ||
| Cav1.4 (Voltage-gated calcium channels (CaV)) |
Cav1.4 and Cav1.3 are involved in CD8+ T cell survival and cytokine production [201,267] ... | ||
| Cav3.1 (Voltage-gated calcium channels (CaV)) |
Low-voltage-activated Cav3.1 calcium channels are involved in shaping the autoimmune response elicited by T cells by modulating their cytokine production profile [278] ... | ||
| P2X7 (P2X receptors) |
P2RX7 is expressed by most immune cells. It elicits an immune response when activated by extracellular ATP that is released by infected or injured cells. P2RX7 expressed on T cells is involved in proliferation, cytokine production, Th17 and T follicular helper cell differentiation and inhibition of Treg differentiation. | The P2X7 receptor is involved in NLRP3-type inflammasome formation, and subsequent maturation of IL-1β [162,215] ... | |
| P2X1 (P2X receptors) |
T cells express P2X receptors 1, 4 and 5. ATP-induced activation of these receptors in T cells is associated with proliferation, cytokine production and thymocyte apoptosis. | Functional P2X1 receptors are expressed by healthy human eosinophils [293] ... | |
| P2X4 (P2X receptors) |
T cells express P2X receptors 1, 4 and 5. ATP-induced activation of these receptors in T cells is associated with proliferation, cytokine production and thymocyte apoptosis. | P2X ligand-gated ion channels elicit pro-inflammatory immune responses upon activation by extracellular ATP that acts as a DAMP when released from damaged or infected cells [40,50] ... | |
| P2X5 (P2X receptors) |
T cells express P2X receptors 1, 4 and 5. ATP-induced activation of these receptors in T cells is associated with proliferation, cytokine production and thymocyte apoptosis. | P2X ligand-gated ion channels elicit pro-inflammatory immune responses upon activation by extracellular ATP that acts as a DAMP when released from damaged or infected cells [40,50] ... | |
| Piezo1 (Piezo channels) |
Piezo1 mechanosensors are involved in the optimisation of human T cell activation and in T cell proliferation. | Work by Liu et al. (2018) shows that Piezo1 is involved in immune regulation [163] ... | |
| TRPM7 (Transient Receptor Potential channels (TRP), ChaK subfamily) |
TRPM7 is essential for T cell development. | Expressed on chicken B cells, mouse T cells, chicken monocytes/macrophages, and human mast cells [205] ... | |
| TRPM4 (Transient Receptor Potential channels (TRP)) |
TRPM4 is involved in T cell cytokine production and motility. | TRPM4 is expressed on human T cells, mouse dendritic cells, human and mouse monocytes/macrophages, and mouse mast cells [205] ... | |
| Nav1.5 (Voltage-gated sodium channels (NaV)) |
Nav1.5 is involved in the positive selection of CD4+ T cells [166] ... | ||
| Enzymes | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| IL2 inducible T cell kinase (Tec family) |
The TEC family protein tyrosine kinases have been identified as key components of T-cell-receptor activation and signalling. TEC family kinases are expressed predominantly by haematopoietic cells. T cells express ITK, TXK and TEC [28] ... | ||
| phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta (Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases) |
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PI3Kδ is preferentially expressed in cells of hemopoietic lineage and is involved in neutrophil chemotaxis. It is the only PI3K isoform with expression restricted to leukocytes. Genetic and pharmacological inactivation of PI3Kδ indicates its importantance for the function of T cells, B cell, mast cells and neutrophils. PI3kδ is a promising target for drugs for preventing or treating inflammation, autoimmunity and transplant rejection [105] ... | |
| cathepsin C (C1: Papain) |
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Cathepsin C (CatC) is a lysosomal cysteine protease that is constitutively expressed at high levels in lung, kidney, liver and spleen. As well as activity in lysosomal protein degradation, cathepsin C also plays a key role in the activation of granule serine proteases in cytotoxic T cells, natural killer cells (granzymes A and B), mast cells (chymase and tryptase) and neutrophils (cathepsin G, neutrophil elastase, proteinase 3). Dysregulated activation of neutrophil elastase at inflammatory sites induces the release of pro-inflammatoy mediators and can lead to acute tissue injury. This mechanism is recognised as causing lung damage in neutrophil driven conditions such as asthma and COPD, and has driven the pharmaceutical industry to search for cathepsin C inhibitors with clinical utility (e.g. brensocatib; formerly AZD7986 and INS1007). SARS-CoV-2 and COVID-19: CatC has been proposed as a drug target to combat ARDS-associated inflammatory lung damage in patients with severe COVID-19. In this setting CatC inhibitors would be expected to protect the lungs from ARDS by reducing the observed virally-induced hyperinflammation that leads to diffuse alveolar collapse and pulmonary tissue damage [144] ... |
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| FYN proto-oncogene, Src family tyrosine kinase (Src family) |
Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [204] ... | ||
| LCK proto-oncogene, Src family tyrosine kinase (Src family) |
Phosphorylation and activation of Lck is an early and critical step in pre-TCR (T cell receptor) and TCR signalling. Activated Lck phosphorylates immunoreceptor tyrosine-based activation motifs of the ζ chain of the TCR leading to recruitment and activation of ZAP-70 tyrosine kinase, and activation of downstream MAPKs and NF-κB. TCR-based signals are required at several stages of T-cell development and it is thought that Lck is the major contributor to TCR signal transduction (with the related Src tyrosine kinase Fyn also playing a role) [204] ... | ||
| enhancer of zeste 2 polycomb repressive complex 2 subunit (2.1.1.43 Histone methyltransferases (HMTs)) |
EZH2 has an inhibitory role in the differentiation of Th1 and Th2 cells. |
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EZH2 is involved in hematopoietic stem cell proliferation and differentiation, thymopoiesis and lymphopoiesis, with notable participation in regulating the differentiation and function of T cells. This role suggests potential applications in immune-mediated conditions, including autoimmune disorders [265] ... |
| dual oxidase 1 (NADPH oxidases) |
DUOX1 expression has been identified in T cells. | DUOX1 participates in innate immune responses to epithelial injury and allergens, and in the development of allergic diseases [269] ... | |
| mitogen-activated protein kinase kinase kinase kinase 1 (KHS subfamily) |
HPK1 (MAP4K1) is highly expressed in hematopoietic cell subsets. It acts as a critical negative regulator in the activation of T cells and dendritic cells [108,241] ... | ||
| mitogen-activated protein kinase kinase kinase kinase 4 (MSN subfamily) |
HGK is widely expressed in different tissues. In vitro, HGK is activated by TNFα stimulation, and this results in JNK activation via the MAP3K, TAK1 (MAP3K7) and the MAP2Ks, MKK4 (MAP2K4) and MKK7 (MAP2K7) [79,253,259] ... | ||
| TRPM7 (Transient Receptor Potential channels (TRP), ChaK subfamily) |
TRPM7 is essential for T cell development. | Expressed on chicken B cells, mouse T cells, chicken monocytes/macrophages, and human mast cells [205] ... | |
| protein tyrosine phosphatase non-receptor type 22 (Protein tyrosine phosphatases non-receptor type (PTPN)) |
Expressed in mature T cells. Expression can be induced in resting peripheral T cells that are activated by phytohemagglutinin or anti-CD3 antibody. | PTPN22 is a lymphoid-specific, inducible protein tyrosine phosphatase [63] ... | |
| protein kinase C theta (Delta subfamily) |
PKDθ is expressed predominantly in T lymphocytes. | PKC-θ is a novel subfamily PKC found predominantly in hematopoietic cells [20] ... | |
| Catalytic Receptors | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| MER proto-oncogene, tyrosine kinase (Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family) |
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Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [25,277] ... | |
| CD30 (Tumour necrosis factor (TNF) receptor family) |
CD30 is expressed by activated, but not by resting, T and B cells. | Expressed by activated T and B cells. Interacts with TRAF2 and TRAF5 to elicit downstream signalling events (NF-κB activation). CD30 may protect against autoimmunity by limiting the proliferative potential of autoreactive CD8 effector T cells. CD30 is the target of the approved anti-lymphoma monoclonal antibody drug brentuximab vedotin ... | |
| Interleukin-7 receptor subunit α (IL-2 receptor family) |
IL-7RA (CD127) is expressed on Teff cells, and is involved in the development and persistence of chronic colitis [240]. |
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This is the ligand binding subunit of the functional IL-7 receptor complex. Effimmune are developing anti-IL7Rα monoclonal antibodies (e.g. OSE-127 [210] ... |
| Transporters | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| Anion exchange protein 2 (Anion exchangers) |
Ae2 expressed by CD8+ T cells is involved in their proliferation and exhaustion and in their capacity to produce IL-2. |
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Ae2 is reported as a critical player in the regulation of CD8+ T cell intracellular pH homeostasis and immune response [64] ... |
| SMCT2 (Sodium iodide symporter, sodium-dependent multivitamin transporter and sodium-coupled monocarboxylate transporters) |
SLC5A12 expression by CD4+ T cells is elevated by lactate accumulation at the sites of chronic inflammation. |
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Lactate accumulation at sites of inflammation has been shown to elevate SLC5A12 expression on CD4+ T cells and increase lactate uptake by the T cells [214] ... |
| Other Protein Targets | |||
| GtoPdb receptor name (family) | Cell Type Association Comments | Cell Ontology Associations | Immunopharmacology Comments |
| programmed cell death 1 (CD279) (Other immune checkpoint proteins, CD molecules) |
PD-1 expression is induced in murine T cells activated by stimulation through antigen receptors. |
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Immune checkpoint blockade in oncology: Many types of cancer cells evolve mechanisms to evade control and elimination by the immune system. Such mechanisms can include inhibition of so-called 'immune checkpoints', which would normally be involved in the maintenance of immune homeostasis. An increasingly important area of clinical oncology research is the development of new agents which impede these evasion techniques, thereby switching immune vigilance back on, and effecting immune destruction of cancer cells. Three molecular targets of checkpoint inhibitors which are being extensively pursued are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1). Using antibody-based therapies targeting these pathways, clinical responses have been reported in various tumour types, including melanoma, renal cell carcinoma [203] ... |
| CD300a (CD molecules) |
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CD300a is a member of the CD300 family of leucocyte surface receptors [35] ... | |
| CD3e (CD molecules) |
CD3e is a subunit of the T cell receptor (TCR)-CD3 complex that mediates T cell receptor signal transduction in response to antigen detection. The TCR complex contains a CD3γ chain (CD3G), a CD3δ chain (CD3D), and two CD3ε chains (CD3E), plus the TCR (that can be α/β, or γ/δ type in the subsets of T cells named after the TCR they express) and the ζ-chain (zeta-chain). CD3e plays a crucial role in T cell development, highlighted by the discovery that defects in CD3e cause severe immunodeficiency [70,245] ... |
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| CD2 (CD molecules) |
CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells [298] ... | ||
| CD6 (CD molecules) |
CD6 is a co-stimulatory molecule, predominantly expressed on lymphocytes and associated with autoimmune responses. CD6 interacts with activated leucocyte-cell adhesion molecule (ALCAM/CD166), found on antigen presenting cells. This interaction induces the production of proinflammatory cytokines [190] ... | ||
| CD28 (Other immune checkpoint proteins, CD molecules) |
CD28 is expressed on the surface of T cells and is required for the co-stimulatory signal essential for the activation, proliferation and survival of T cells, and Th2 cell development. CD28 acts in concert with the T cell receptor to stimulate cytokine release (promotes IL-2 production). CD28 binds the the B7 proteins CD80 and CD86 on the surface of antigen presenting cells to effect a co-stimulatory signal to T cells. In contrast, CTLA-4 delivers a co-inhibitory signal via CD80/CD86 [7] ... | ||
| CD38 (Abscisic acid receptor complex, CD molecules) |
CD38 is a type II transmembrane glycoprotein, that is widely expressed on immune cells and is involved in cell adhesion and signal transduction. Its extracellular domain acts as an ectoenzyme, catalyzing the conversion of nicotinamide adenine dinucleotide (NAD+) into nicotinamide, adenosine diphosphate-ribose (ADPR), and cyclic ADPR. Expression of CD38 is tightly regulated during B-cell development and maturation [103] ... | ||
| CD52 (CD molecules) |
CD52 (CAMPATH-1) is a short, glycosylphosphatidylinositol (GPI) anchored peptide expressed on lymphocytes and by cells of the male genital tract. CD52 is required for complement-mediated cell lysis and antibody-mediated cellular cytotoxicity. The approved monoclonal antibody, alemtuzumab ... | ||
| CD74 (CD molecules) |
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CD74 is a type II transmembrane glycoprotein which associates with the MHC class II α and β chains and directs the transport of class II molecules to lysosomal and endosomal compartments [67] ... | |
| CD80 (Other immune checkpoint proteins, CD molecules) |
CD80 (B7-1) is expressed on dendritic cells and activated B cells and monocytes. It is required to provide a costimulatory signal necessary for T cell activation and survival. CD80 works in concert with CD86 to prime T cells. CD80 binds CD28 and CTLA-4 on T cells. It is the interaction with CTLA-4 t ... | ||
| CS1 (CD319) (CD molecules) |
CS1 is a member of the signalling lymphocyte activation molecule (SLAM) receptor family. CS1 is a membrane glycoprotein primarily expressed on plasma cells. Homophilic interaction (i.e. interaction with itself) of CS1 induces B cell proliferation and autocrine cytokine secretion, thus playing a role in various immune functions. CS1 is a validated molecular target for the development of novel immunotherapeutics with the potential to treat MM, a malignant disease of plasma cells which remains incurable despite advances in treatment (such as bortezomib, lenalidomide and immunotherapies in clinical trial). Indeed, a combination therapy containing the anti-CS1 mAb elotuzumab (elotuzumab + lenalidomide + dexamethasone), was FDA approved for MM in 2015. CS1 expression is also elevated in patients with systemic lupus erythematosus (SLE) [140] ... |
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| regulator of G-protein signaling 1 (R4 family) |
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RGS1 is expressed in lymphocytes and macrophages and plays a role in leukocyte trafficking and vascular inflammation [36,104,186,206] ... | |
| LAG3 (CD223) (Other immune checkpoint proteins, CD molecules) |
LAG3 is an activation marker for CD4+ and CD8+ T cells. |
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Membrane-bound LAG3 (CD223) is a T cell inhibitory co-receptor and immune checkpoint being investigated as a cancer immunotherapeutic target [10,98] ... |
| TIM3 (CD366) (Other immune checkpoint proteins, CD molecules) |
TIM3 is a selective marker of differentiated Th1 cells. Upregulation of TIM3 expression is reported as a biomarker associated with adaptive resistance to PD-1 blockade. |
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TIM3 is an immunoglobulin type protein expressed exclusively on the surface of differentiated Th1 cells [185] ... |
| TIGIT (Other immune checkpoint proteins, Immunoglobulin like domain containing proteins) |
Expressed on regulatory, memory and activated T cells. | TIGIT is now considered as an alternate inhibitory immune checkpoint protein which may have potential immunotherapeutic potential, particularly in conditions refractory to more established PD-1 checkpoint inhibition. Given its presence on T cells and NK cells, TIGIT offers an intervention point for targeting both the adaptive and innate arms of the immune system. Clinical development of anti-TIGIT monoclonal antibodies is in preliminary stages. Combination therapies with existing immune checkpoint inhibitors are considered particularly promising. MTIG7192A (NCT02794571 ... | |
| V-set immunoregulatory receptor (Other immune checkpoint proteins) |
Expressed on Foxp3+CD4+ regulatory T cells. |
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V-set immunoregulatory receptor (VSIR) is commonly referred to as VISTA in the literature corpus. This is an Ig superfamily (B7 family) protein that acts as an inhibitory immune-checkpoint molecule. In common with other T cell co-inhibitory receptors (e.g. CTLA-4, PD-1, TIM3, and LAG3) it is involved in maintaining peripheral tolerance [158] ... |
| ICOS (CD278) (Other immune checkpoint proteins, CD molecules) |
ICOS is upregulated on effector and memory T cells during activation. It is also present on peripheral Tregs. |
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Inducible T cell costimulator (ICOS) and it's ligand constitute an immune checkpoint. ICOS is a surface receptor on activated T cells that binds its ligand on antigen presenting cells. Ligand-receptor interaction is a T cell activation signal. ICOS is a major regulator of the adaptive immune reponse that is structurally and functionally related to CD28 [117] ... |
| chitinase 3 like 1 (Chitinase-like proteins) |
mRNA and protein levels of Chi3l1 are strongly induced following anti-CD3 and anti-CD28 stimulation of T cells, and Chi3l1 is selectively induced in Th0 and Th2 cells compared to other effector T cell subsets. | CHI3L1 is recognised as a proinflammatory mediator in the development and progression of Th2 inflammation, such as in allergic reactions [44] ... | |
| CD4 (CD molecules) |
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CD4 is being targeted for clinical utility in inflammatory diseases like rheumatoid arthritis (RA), neoplasms derived from T helper cells (T cell lymphomas and related malignancies), and for anti-HIV potential. Depending on the design of CD4 targeting antibodies, they can produce immunosuppressive effects via activation of Tregs and induction of tolerance, block HIV binding to CD4 to prevent HIV infection, or induce depletion of CD4+ T cells by apoptosis, ADCC, or CDC [143,274] ... | |
| CD37 molecule (CD molecules, Tetraspanins) |
CD37 expression by T cells and myeloid cells is lower than expression by mature B cells. | CD37 is included in GtoImmuPdb as it is an immuno-oncology target that is being expoited for the development of novel therapeutics for the treatment of B cell malignancies, including non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) [73,202,251,291] ... | |
| neuropilin 1 (Neuropilins and Plexins) |
Neuropilin 1 is expressed by Treg cells and promotes their function and survival. |
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NRP1 is expressed on several types of immune cells (e.g. T cells, dendritic cells) [223,263] ... |
| PVR related immunoglobulin domain containing (Other immune checkpoint proteins) |
PVRIG is constitutively expressed by human and murine NKT cells. | PVRIG has been identified as a novel co-inhibitory immune checkpoint, that is exploited by some cancer cells to evade immune detection [187,288] ... | |
| S100 calcium binding protein A11 (EF-hand domain containing proteins) |
S100A11 is a pro-inflammatory calcium-binding protein. Elevated S100A11 has been reported as a marker of disease activity and extramuscular manifestations in inflammatory myopathies [11] ... | ||
| perforin 1 (Cytolytic pore-forming proteins) |
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Perforin 1 is expressed only in the secretory granules of cytotoxic T cells and natural killer (NK) cells, and it is an essential component of the immune system. These cell types release perforin 1 close to target cells (e.g. virus-infected and neoplastic cells) in process known as the granule exocytosis pathway [71] ... | |
| regulator of G-protein signaling 10 (R12 family) |
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| CD24 molecule (CD molecules) |
CD24 is a small GPI-anchored sialoglycoprotein that is expressed by immune cells. It is involved in B cell and T cell functions. CD24 binds to SIGLEC10 in an interaction that selectively suppresses the immune response to danger-associated molecular patterns (DAMPs). This latter action is being explo ... | ||
