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Targets Associated with Immuno Processes - Antigen presentation
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| Antigen presentation | Download as CSV | |||
Targets Associated to Immuno Processes
Full documentation can be found in the GtoImmuPdb immuno cell type data documentation (PDF). ✖ |
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| GPCRs | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| ACKR2 (Chemokine receptors) |
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ACKR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. | ||
| ACKR3 (Chemokine receptors) |
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ACKR3 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. ACKR3 binds the chemokine CXCL12 (stromal cell-derived factor 1, SDF-1 which is also a ligand for CXCR4). ACKR3 is an atypical receptor in that it does not activate G-protein-mediated signaling but induces β-arrestin recruitment [103] ... | ||
| ACKR4 (Chemokine receptors) |
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ACKR4 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. | ||
| apelin receptor (Apelin receptor) |
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The apelin receptor gene (APLNR) has been identified as one of a number of genes necessary to confer suceptibility of cancer cells to immunotherapy (i.e. T cell recognition and cytolysis) [158] ... | ||
| A1 receptor (Adenosine receptors) |
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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 ... | ||
| A2A receptor (Adenosine receptors) |
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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 [207] ... | ||
| β2-adrenoceptor (Adrenoceptors) |
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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 [66] ... | ||
| CCR2 (Chemokine receptors) |
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CCR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CCR2 is discussed in relation to immuno-oncology in [3] ... | ||
| CCR7 (Chemokine receptors) |
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CCR7 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. | ||
| CXCR1 (Chemokine receptors) |
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CXCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR1 is discussed in relation to immuno-oncology in [3] ... | ||
| CXCR2 (Chemokine receptors) |
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CXCR2 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR2 is discussed in relation to immuno-oncology in [3] ... | ||
| D2 receptor (Dopamine receptors) |
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D2 receptor-mediated anti-inflammatory effects in the kidney have a protective effect. In contrast, impaired D2 receptor function results in renal inflammation and organ damage [238] ... | ||
| FPR2 (Formylpeptide receptors, Leukotriene receptors) |
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Formyl peptide receptor type 2 (FPR2/ALX) activation by lipoxin A4 and annexin 1 has been linked to resolution of inflammation, via upregulation of anti-inflammatory cytokines including IL-10. Resolvin D1-mediated activation of FPR2/ALX appears to resolve salivary gland inflammation in a mouse model of Sjögren syndrome [216] ... | ||
| P2Y6 receptor (P2Y receptors) |
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P2Y6R expression on airway epithelial cells is up-regulated during acute and chronic allergic airway inflammation, and selective antagonism of P2Y6R reduces typical features of experimental asthma [211] ... | ||
| PAR2 (Proteinase-activated receptors) |
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PAR2 receptors have been reported to elicit pain and inflammation through a neurogenic mechanism of action, causing release of substance P, activation of NK1 receptors, and sensitization of TRPV1 voltage-gated ion channels. This action can be negated using a selective NK1 receptor antagonist (L732,138) or a TRPV1 receptor antagonist (capsazepine) [77] ... | ||
| Ion Channels | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| KCa3.1 (Calcium- and sodium-activated potassium channels (KCa, KNa)) |
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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 [64,70,136] ... | ||
| P2X7 (P2X receptors) |
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The P2X7 receptor is involved in NLRP3-type inflammasome formation, and subsequent maturation of IL-1β [126,169] ... | ||
| Nuclear Hormone Receptors | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| Liver X receptor-α (1H. Liver X receptor-like receptors) |
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Liver X receptors (LXR) are involved in the regulation of lipid metabolism and inflammatory responses. As such they are novel drug targets for cholesterol homeostasis (hypercholesterolaemia), inflammation, and with potential therapeutic effects in neurodegenerative diseases [228] ... | ||
| Liver X receptor-β (1H. Liver X receptor-like receptors) |
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Liver X receptors are involved in the regulation of lipid metabolism and inflammatory responses. LXRs are drug targets for cholesterol homeostasis (hypercholesterolaemia), inflammation, and with therapeutic potential in neurodegenerative diseases [228] ... | ||
| Enzymes | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| ABL proto-oncogene 1, non-receptor tyrosine kinase (Abl family) |
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Included in GtoImmuPdb based on its association with leukemia. | ||
| autotaxin (LPA synthesis) |
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Autotaxin is up-regulated in many inflammatory conditions, including cancer, arthritis, fibrotic diseases and multiple sclerosis. The product of autotaxin activity, LPA, has proliferative, chemotactic and angiogenic actions. Inhibitors of the ATX-LPA axis are being investigated as novel pharmaceuticals [46] ... | ||
| beta adrenergic receptor kinase 1 (Beta-adrenergic receptor kinases (βARKs)) |
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GRK2 (βARK1) expression and activity are downregulated in lymphocytes from RA patients [130] ... | ||
| Bruton tyrosine kinase (Tec family) |
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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 [26] ... | ||
| cathepsin H (C1: Papain) |
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Cathepsin H may act as a pro-granzyme B convertase [59] ... | ||
| cathepsin L (C1: Papain) |
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Cathepsins B, H and L have become important therapeutic targets as their proteolytic activity has been implicated in several pathological inflammatory conditions, such as arthritis and periodontitis. Therefore, pharmacological inhibitors of these enzymes are in development as novel therapeutics. | ||
| cathepsin S (C1: Papain) |
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Cathepsin S is expressed in the lysosome of antigen presenting cells (dendritic cells, B-cells and macrophages) where it processes the invariant chain-MHC-II complex (a chaperone protein that prevents premature peptide loading) inside antigen presenting cells and in this way controls antigen presentation. Due to this role in antigen presentation, inhibition of cathepsin S is expected to cause immunosuppression [198] ... | ||
| Cbl proto-oncogene B (E3 ubiquitin ligase components) |
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Cbl-b is an E3 ubiquitin ligase that is involved in regulating T cell activation and peripheral T cell tolerance [122,128] ... | ||
| C-terminal Src kinase (Csk family) |
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CSK is an inhibitory regulator of Src family kinases, a family of protein tyrosine kinases indispensable to the initiation of signal transduction via ITAM-bearing immunoreceptors, and cytokine, growth factor, and pattern recognition receptor signalling. CSK phosphorylates an inhibitory tyrosine residue at the C terminus of Src kinases, leading to autoinhibition. CSK-induced Src kinase inhibition can also be mediated by binding to PEST family receptor tyrosine phosphatases [208] ... | ||
| ectonucleotide pyrophosphatase/phosphodiesterase 1 (Cyclic GMP-AMP turnover) |
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ENPP1 is a promising therapeutic target in tumour immunotherapy, with inhibitors offering potential to boost the anti-tumour immune response. | ||
| elastase, neutrophil expressed (S1: Chymotrypsin) |
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Neutrophil elastase (NE) is a serine proteinase with broad substrate specificity. It is stored in azurophil granules within neutrophils and is involved primarily in host defence. However, in addition to attacking proteins on invading microorganisms, secreted NE also hydrolyzes proteins of the host extracellular matrix, such as collagen-IV and elastin, hence its role in degenerative and inflammatory diseases. NE functions as a promoter of γδ T cell activation via a protease-activated receptor (PAR1)-dependent mechanism [202] ... | ||
| FGR proto-oncogene, Src family tyrosine kinase (Src family) |
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Fgr may be involved in neutrophil migration, potentially via binding to intergrins [21] ... | ||
| FYN proto-oncogene, Src family tyrosine kinase (Src family) |
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Animal models and cell line studies indicate a critical role for Fyn in proximal T-cell antigen receptor (TCR) signal transduction [154] ... | ||
| Haem oxygenase 1 (Haem oxygenase) |
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Heme oxygenase (HO) is a rate-limiting enzyme in the catabolism of heme, catalyzing the oxidative cleavage of heme (Fe-protoporphyrin-IX) to render equimolar amounts of biliverdin, ferrous iron (Fe2+), and carbon monoxide (CO). Heme oxygenase 1 (HO1) is a Nrf2-regulated gene, whose expression is upregulated as a cytoprotective mechanism in response to cellular stresses including inflammation, ischemia, hypoxia, hyperoxia, hyperthermia, or radiation. HO1 has antioxidant, antiinflammatory, antiapoptotic, antiproliferative, and immunomodulatory effects in vascular cells, playing an important role in the prevention of vascular inflammation and atherogenesis (reviewed in [9] ... |
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| HCK proto-oncogene, Src family tyrosine kinase (Src family) |
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Hck is thought to be involved in neutrophil migration, potentially via binding to intergrins [21] ... | ||
| Inducible NOS (Nitric oxide synthases) |
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The role of iNOS in immuno-oncology is reviewed in [3] ... | ||
| inhibitor of nuclear factor kappa B kinase subunit beta (IKK family) |
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Iκβ kinase β (IKK-2) is the pivotal enzyme component of the Iκβ kinase (IKK) complex, a complex crucial in regulating expression and activation of inflammatory mediators in airway epithelium. IKK-2 is an attractive target for development of pharmaceutical inhibitors with antiinflammatory action as treatments for asthma and chronic obstructive pulmonary disease (COPD) [24,29,190] ... | ||
| LYN proto-oncogene, Src family tyrosine kinase (Src family) |
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LYN is a Src family tyrosine kinase, expressed predominantly in hematopoietic cells, but also in neural, liver, and adipose tissues. LYN appears to function as a rheostat to modulate B cell signaling, and can be activating or inhibitory in action, depending on the B cell receptor and interacting protein complement present in particular cells [72,75,201] ... | ||
| mitogen-activated protein kinase 1 (ERK subfamily) |
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In endothelial cells of the vasculature, and in activated human mast cells, ERK serves as an anti-inflammatory signal that suppresses production of pro-inflammatory mediators [109,133] ... | ||
| p21 (RAC1) activated kinase 1 (PAKA subfamily) |
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PAK1 is reported to modulate a pro-inflammatory PPARγ/NF-κB cascade in intestinal inflammation, that may be relevant in inflammatory bowel disease and colitis-associated cancer [61] ... | ||
| phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases) |
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PI3Kα is primarily recognised for its oncogenic function. We have included it in GtoImmuPdb based on its numerous GO immune process associations. | ||
| phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (Phosphatidylinositol-4,5-bisphosphate 3-kinase family, Phosphatidylinositol kinases) |
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The role of PI3Kγ in immuno-oncology is reviewed in [3] ... | ||
| phosphoinositide kinase, FYVE-type zinc finger containing (1-phosphatidylinositol-3-phosphate 5-kinase family) |
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PIKfyve is a class III PI kinase. Evidence is revealing a crucial role for PIKfyve in Toll-like receptor (TLR) signaling via production of the cytokines IL-12 and IL-23 [44] ... | ||
| PLCγ2 (Phosphoinositide-specific phospholipase C) |
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Two structurally similar isoforms of PLCγ are expressed by mast cells (PLCγ1 and PLCγ2). Both are important enzymes in the integrated signalling pathways leading to mast cell activation [81,179] ... | ||
| proteasome 20S subunit beta 8 (T1: Proteasome) |
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PSMB8 is a component of the immunoproteasome [69] ... | ||
| proteinase 3 (S1: Chymotrypsin) |
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Proteinase 3 (PR3), called myeloblastin when it was first identified, is an abundant serine protease found principally in neutrophil granules (but is also found on the surface of quiescent human neutrophils from peripheral blood). It is stored in the primary granules of circulating neutrophils alongside other cathepsin C-activated neutrophil serine proteases (NSPs), such as human neutrophil elastase (HNE), CatG, and NSP4. In pathological conditions it is thought that PR3 behaves to accelerate inflammation, by enhancing cytokine bioactivity, inactivating anti-inflammatory mediators and by promoting tissue injury (potentially by degrading extra-cellular matrix components like elastin, collagen, fibronectin, and laminins). In addition, imbalances between NSPs and their endogenous inhibitors can contribute towards pathological tissue damage, such as the damage associated with inflammatory lung diseases like chronic obstructive pulmonary disease (COPD), emphysema, and cystic fibrosis. PR3 inhibitors are considered to be useful clinical candidates for anti-inflammatory drug development [112] ... | ||
| protein kinase C delta (Delta subfamily) |
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PKCδ is included in GtoImmuPdb based on its GO immune process associations. | ||
| protein kinase C epsilon (Eta subfamily) |
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PKCε is included in GtoImmuPdb based on its GO immune process associations. | ||
| protein kinase C gamma (Alpha subfamily) |
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PKCγ is included in GtoImmuPdb based on the involvement of other PKC isozymes in immune processes. | ||
| protein tyrosine kinase 2 (Fak family) |
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FAK and Pyk2 are phosphorylated downstream of the T cell antigen receptor (TCR) to bring about receptor-specific T cell development and activation [50] ... | ||
| protein tyrosine phosphatase non-receptor type 1 (Protein tyrosine phosphatases non-receptor type (PTPN)) |
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Inhibition of PTPN1/2 promotes T cell-mediated anti-tumour immunity [23,124,240] ... | ||
| protein tyrosine phosphatase non-receptor type 2 (Protein tyrosine phosphatases non-receptor type (PTPN)) |
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Inhibition of PTPN1/2 promotes T cell-mediated anti-tumour immunity [23,124,240] ... | ||
| RAB27A, member RAS oncogene family (RAB subfamily) |
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Small molecule inhibitors of Rab27a-JFC1 binding, termed Nexinhibs (neutrophil exocytosis inhibitors) demonstrate the druggability of Rab GTPases and inhibition of exocytosis of azurophilic granules in human neutrophils without affecting other important innate immune responses, including phagocytosis and neutrophil extracellular trap production. These thus have potential use as an inhibitor of systemic inflammation [102] ... | ||
| sphingosine kinase 1 (Sphingosine kinase) |
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The sphingosine kinases (SPHK1 and SPHK2; SK1, SK2) are key enzymes within the sphingolipid metabolism pathway that promote tumour growth and pathologic inflammation. SK1-selective inhibitors include PF-543 [182-183] ... | ||
| spleen associated tyrosine kinase (Syk family) |
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SYK plays a key role in coupling activated immunoreceptors to downstream cellular responses such as proliferation, differentiation, and phagocytosis. Mast cell, macrophage and B-cell activation (and release of inflammatory modulators) is disrupted by inhibition of SYK-mediated immunoreceptor signalling. Selective SYK inhibitors are being sought for a number of inflammatory conditions including rheumatoid arthritis, B-cell lymphoma and asthma/rhinitis [79,172] ... | ||
| SRC proto-oncogene, non-receptor tyrosine kinase (Src family) |
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Src family tyrosine kinases act as general modulators of immune cell signaling, playing diverse signaling functions, both inhibitory and stimulatory, in immunoreceptor and integrin signaling pathways [131] ... | ||
| transglutaminase 2 (2.3.2.13 Transglutaminases) |
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TGM2 upregulation by amyloid β (Aβ)1-42 in THP-1 monocytes increases pro-inflammatory mediators, including IL-1β and IL-6. A transglutaminase inhibitor can blunt this activation, suggesting that TGM2 up-regulation is involved in the pro-inflammatory effect of Aβ1-42 on monocytes [57] ... | ||
| YES proto-oncogene 1, Src family tyrosine kinase (Src family) |
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Although primarily recognised for its oncogenic activity, we have iincluded YES1 in GtoImmuPdb based on its expression in cells of the immune system. | ||
| Catalytic Receptors | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| AXL receptor tyrosine kinase (Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family) |
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All three TAM family receptor tyrosine kinases are involved in regulating inflammatory responses through a negative feedback loop. Specifically, AXL-Gas6 signalling is reported to induce autophagy in murine macrophages via inhibition of the NLRP3 inflammasome, an effect which reduces hepatic inflammation in a mouse model [85] ... | ||
| Fc fragment of IgE receptor Ig (Fc epsilon receptors) |
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The FCER1G protein is a gamma subunit that is utilised as part of the high affinity IgE receptor (a key complex involved in mediating allergic reactions) and other Fc receptors. | ||
| Fc fragment of IgE receptor II (Fc epsilon receptors) |
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FcεRII (CD23) is the low-affinity receptor for immunoglobulin E (IgE) with a Kd > 100nM. This protein is a C-type lectin found on mature B cells, activated macrophages, eosinophils, follicular dendritic cells, and platelets. It has no structural similarities with other Fc receptors. FcεRII has functions as both a membrane-bound and as a soluble receptor [107,232] ... | ||
| integrin, alpha 4 subunit (antigen CD49D, alpha 4 subunit of VLA-4 receptor) (Integrins) |
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Integrin subunit alpha 4 is the alpha subunit of the α4β1 lymphocyte homing receptor. The cytoplasmic domain of α4 binds tightly to paxillin, a signaling adaptor protein, and this interaction promotes increased cell migration and inhibits cell spreading [86] ... | ||
| integrin, alpha L subunit (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide) (Integrins) |
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ITGAL associates with the beta 2 chain (ITGB2) integrin and CD18 to form the lymphocyte function-associated antigen-1 (LFA-1) complex. LFA-1 is crucial for leukocyte intercellular adhesion and costimulatory signaling in the immune system. Ligands for LFA-1 are the intercellular adhesion molecules (ICAMs) 1-3. ITGAL is the target of the withdrawn psoriasis monoclonal antibody drug efalizumab ... | ||
| integrin, beta 2 subunit (complement component 3 receptor 3 and 4 subunit) (Integrins) |
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ITGB2 is the beta component of the β2 integrins. It forms αβ heterodimers with the CD11 alpha subunits ITGAL (αL aka CD11a forming integrin LFA-1), ITGAM (αM aka CD11b, forming integrin Mac-1) and ITGAX (αX aka CD11c, forming integrin p150/95). Beta2-integrins are essential for leukocyte extravasation to sites of infection (i.e. leukocyte trafficking), and other immunological processes including neutrophil phagocytosis and ROS production, and T cell activation. Their absence causes a leukocyte adhesion deficiency, which manifests clinically as recurrent severe infections, defective wound healing and neutrophilia [111] ... | ||
| Interleukin 10 receptor, α subunit (IL-10 receptor family) |
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Interleukin 10 receptor, α subunit is a component of the functional IL-10 receptor heterodimer. | ||
| Interleukin-15 receptor subunit α (IL-2 receptor family) |
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This is the ligand binding subunit of the functional IL-15 receptor complex. | ||
| Interleukin-2 receptor subunit β (IL-2 receptor family) |
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IL2RB is a ligand binding component of the IL-2R and is required to elevate ligand affinity. It also a component of the IL-15R. | ||
| Interleukin-2 receptor subunit γ (IL-2 receptor family) |
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IL2RG is a common signal transducing subunit shared by the receptors for several different cytokines, namely the IL-2 receptor heterotrimer, the IL-4 receptor type I, the IL-7 receptor, the IL-9 receptor, the IL-15 receptor and the IL-21 receptor. | ||
| macrophage stimulating 1 receptor (Type X RTKs: HGF (hepatocyte growth factor) receptor family) |
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The role of RON in immuno-oncology is reviewed in [3] ... | ||
| 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 [25,215] ... | ||
| nucleotide binding oligomerization domain containing 1 (NOD-like receptor family) |
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NOD1 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing a D-glutamyl-meso-diaminopimelic acid (iE-DAP) moiety. Mutations in NOD proteins are implicated in various inflammatory diseases associated with aberrant NF-κB activ ... |
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| nucleotide binding oligomerization domain containing 2 (NOD-like receptor family) |
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NOD2 is an intracellular pattern recognition receptor that initiates an immune response to bacterial molecules containing muramyl dipeptide (MDP). Mutations in NOD proteins are implicated in various inflammatory diseases associated with aberrant NF-κB activity; NF-κB being a major ... |
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| RTP Type C (Receptor tyrosine phosphatase (RTP) family) |
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CD45 is a high molecular weight cell surface glycoprotein expressed by cells of hematopoietic origin. Alternate transcripts lead to expression of isoforms that differ in their extracellular (ligand binding) domain (potentially facilitating differential and/or cell type specific biological functions [60] ... | ||
| TLR2 (Toll-like receptor family) |
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TLR1/2 and 2/6 heterodimers detect and initiate an immune response to triacylated and diacylated [143] ... | ||
| TLR4 (Toll-like receptor family) |
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TLR4 selectively responds to bacterial endotoxin, Gram-negative bacterial lipopolysaccharides (LPS), and lipooligosaccharides (LOS) [27,165] ... | ||
| TYRO3 protein tyrosine kinase (Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family) |
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TYRO3 is a negative regulator of type 2 immunity [49] ... | ||
| Transporters | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| ABCB3 (ABCB subfamily) |
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TAP1 (ABCB2) and TAP2 (ABCB3) form a transporter that plays an important role in antigen presentation by major histocompatibility complex class I (MHCI) molecules in the adaptive immune response [185] ... | ||
| NRAMP1 (SLC11 family of proton-coupled metal ion transporters) |
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NRAMP1 / SLC11A1 appears to be involved in macrophage antimicrobial action against intracellular pathogens, and although its precise mechanism is not fully resolved, evidence indicates its involvement in the activation of phagocytes and synthesis of proinflammatory cytokines. Polymorphisms in the human SLC11A1 gene have been associated with susceptibility to several infections [37,191,193] ... | ||
| Other Protein Targets | ||||
| GtoPdb receptor name (family) | Process Association Comments | GO Associations | Immunopharmacology Comments | |
| advanced glycosylation end-product specific receptor (Immunoglobulin like domain containing proteins) |
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RAGE is a single chain, membrane bound immunoglobulin type protein [145,180,230] ... | ||
| Bcl-2-like 1 (B-cell lymphoma 2 (Bcl-2) protein family) |
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The role of Bcl-2 family members in immunity and disease is reviewed in [5] ... | ||
| CD14 molecule (CD molecules) |
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Because of its key role in amplifying the immune response, CD14 was targeted for pharmacological modulation. Implicit Bioscience developed a first-in-class anti-CD14 monoclonal antbody (atibuclimab; IC14) as a clinical lead [194,210] ... | ||
| CD1d molecule (CD molecules) |
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CD1d is a lipid-binding MHC class I-like protein that is expressed by dendritic cells. CD1d presents self and microbial lipid/glycolipid antigens to unconventional T cells known as invariant natural killer T (iNKT) cells [51,225] ... | ||
| CD209 molecule (C-type lectin-like receptors (CLRs)) |
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DC-SIGN is a pathogen-recognition receptor involved in initiating the primary immune response to various viral and bacterial pathogens, as well as antigen presentation and initiation of the adaptive immune response. | ||
| CD22 (Other immune checkpoint proteins, CD molecules, SIGLECs (conserved)) |
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CD22 (SIGLEC2) is a B cell I-type (Ig-type) lectin that binds glycans containing sialic acids. It is involved in adhesion and activation, mediates B cell-B cell interactions and may be involved in the localisation of B cells in lymphoid tissues. Most SIGLECs inhibit immune cell activation, via | ||
| CD300a (CD molecules) |
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CD300a is a member of the CD300 family of leucocyte surface receptors [32] ... | ||
| CD36 molecule (CD36 blood group) (CD molecules) |
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CD36 expressed by macrophages plays a key role in the recognition and phagocytosis (scavenging) of multiple ligands that are recognised either as damage-associated molecular patterns (DAMPs) released by apoptotic cells, or as potentially dangerous pathogen-associated ligands. CD36 associates with specific Toll-like receptor (TLR) DAMP-detecting heterodimers when bound by certain ligands, and following internalisation of the ligand/CD36/TLR clusters, inflammatory responses (e.g. NF-κB-dependent production of CXCL1, CXCL2, CCL9 and CCL5, NLRP3 inflammasome-mediated IL-1B production, and NF-κB-dependent production of TNF in reponse to microbial diacylated lipopeptide) are triggered. Pharmacological modulation of CD36/TLR signalling is being explored as a strategy to suppress macrophage-driven inflammation [62,203,237] ... | ||
| CD47 (CD molecules) |
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CD47 belongs to the immunoglobulin superfamily and is reported to bind membrane integrins and the ligands thrombospondin 1 (THBS1) and signal-regulatory protein alpha (SIRPα). It is a ubiquitously expressed membrane protein that is a 'marker of self', and it is involved in self tolerance. Binding to SIRPα produces an anti-phagocytic signal. The CD47/THBS1 axis has been implicated in wound healing, and in the pathological progression of immune thrombocytopenia (ITP) [231] ... |
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| 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 [56] ... | ||
| C-type lectin domain family 4 member A (C-type lectin-like receptors (CLRs)) |
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CLEC4A is an pattern recognition receptor and immunoreceptor that functions in cell adhesion, cell-cell signalling, glycoprotein turnover, and plays roles in inflammation and the immune response. It contains a immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic domain. | ||
| C-type lectin domain family 7 member A (C-type lectin-like receptors (CLRs)) |
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Dectin-1 is a pattern recognition receptor involved in initiating the innate immune response upon recognition of various β(1,3)-linked and β(1,6)-linked glucans from fungi and plants. It mediates phagocytosis and the production of inflammatory mediators [38] ... | ||
| Fc fragment of IgM receptor (Immunoglobulin like domain containing proteins) |
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FcμRI is the cognate Fc receptor for immunoglobulin M (IgM) [115,129,186] ... | ||
| immunoglobulin heavy constant epsilon (Immunoglobulins) |
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IgE is being investigated as a molecular target in allergic inflammatory conditions such as asthma, allergic rhinitis and chronic spontaneous urticaria. One anti-IgE monoclonal, omalizumab, has already been approved for use in patients with asthma or chronic spontaneous urticaria. Omalizumab binds t ... | ||
| leukocyte immunoglobulin like receptor B1 (CD85j) (CD molecules, Other immune checkpoint proteins) |
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LILRB1 (CD85j) is a member of the inhibitory leukocyte immunoglobulin like receptor (LILRB) family (HGNC family 1182). It acts as an inhibitory immune checkpoint for B cell function. Ligands identified for LILRB include native MHC class I proteins, some HLA molecules, pathogen-derived ligands (e.g. from CMV, Dengue virus and some bacteria) and host immunomodulatory proteins such as S100 calcium binding protein A9 (S100A9; P06702; which also binds TLR4 and RAGE) [39] ... | ||
| lymphocyte antigen 75 (Lymphocyte antigens) |
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Lymphocyte antigen 75 (CD205) is a surface multilectin receptor. It acts as an endocytic receptor in dendritic and thymic epithelial cells that is crucial for processes that facilitate antigen uptake and processing. Expressed in hematopoietic cells (esp. dendritic cells) [41] ... | ||
| signal transducer and activator of transcription 3 (STAT transcription factors) |
|
STAT3 regulates the expression of a variety of genes in response to cytokines and growth factors (e.g. IFNs, EGF, IL-5, IL-6, HGF, LIF and BMP2) and plays important roles in several cellular processes, including cell growth and apoptosis. STAT3 is a crucial component of the JAK/STAT signalling pathway that is implicated in cancer and inflammation. STAT3 is frequently activated in cancers, where it downmodulates intrinsic immune surveillance of tumour cells. Phosphorylated (activated) STAT3 (pSTAT3) is a marker of poor cancer prognosis [233,235] ... | ||
| SIRPA (CD172a) (CD molecules, Signal regulatory proteins) |
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SIRPα is an important inhibitory immune response regulator. In interaction with CD47, SIRPα controls an inhibitory innate immune checkpoint that provides an anti-phagocytic (do not eat) signal. SIRPα is predominantly expressed by macrophages. Laboratory work has established that SIRPα is expressed by a subset of intestinal dendritic cells (integrin CD103+ DCs) that are critical for maintaining intestinal (mucosal) immune system homeostasis. This subset of CD103+SIRPα+ DCs selectively activates Th17 cells and type 3 innate lymphoid cells (ILC3) [101,220] ... | ||
| stabilin 1 (Scavenger receptors) |
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Stabilin-1/CLEVER-1 scavenges and clears unwanted self components, and promotes immunosuppression in the tumour microenvironment. Expression on macrophages and endothelial cells is induced during chronic inflammation. Blocking Stabilin-1 on monocytes or macrophages converts immunosuppressive M2 macrophages into immunostimulatory M1 macrophages, and this effect is being investigated as a mechanism to induce T cell-dependent killing of cancer cells [93,212] ... | ||
| unc-119 lipid binding chaperone (Lipid binding chaperones) |
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UNC119's role in regulating lymphocyte-specific protein tyrosine kinase (Lck) activity has been reported to be essential for the formation of immunological synapses and activation of T cells [84] ... | ||
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