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Targets Associated to Immuno Cell Types - T cells

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The T cells category includes the following Cell Ontology parent terms:

alpha-beta T cell (CL:0000789) - A T cell that expresses an alpha-beta T cell receptor complex.
effector T cell (CL:0000911) - A differentiated T cell with ability to traffic to peripheral tissues and is capable of mounting a specific immune response.
regulatory T cell (CL:0000815) - A T cell which regulates overall immune responses as well as the responses of other T cell subsets through direct cell-cell contact and cytokine release.

This should encompass most cytotoxic and helper T cells, as well as regulatory T cells.

GPCRs
GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
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 discussed in this immuno-oncology review [2] ...
    β2-adrenoceptor
    (Adrenoceptors)
    CD8+ T cells from patients with rheumatoid arthritis express lower levels of β2-ARs compared with healthy subjects.
    • CD8-positive, alpha-beta T cell (CL:0000625)
    β2-ARs are expressed on innate and adaptive immune cells of humans and rodents, and are reported to have an immuno-modulating effect [29] ...
    CCR3
    (Chemokine receptors)
    CCR3 is expressed on mast cells, basophils, and Th2 lymphocytes.
    • T-helper 2 cell (CL:0000546)
    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.
    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 [46] ...
      5-HT1B receptor
      (5-Hydroxytryptamine receptors)
      Involved in T cell proliferation.
        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 [16] ...
          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 [4] ...
            GPR15
            (Class A Orphans)
            • T-helper 2 cell (CL:0000546)
            Several lines of evidence suggest that GPR15 is a chemoattractant receptor supporting the trafficking of T effector cells to the colon [34,62] ...
            NK1 receptor
            (Tachykinin receptors)
            T helper cells
              Expression in monocytes, macrophages and T helper cells suggests a role in inflammation/immunity.
              FFA3 receptor
              (Free fatty acid receptors)
                FFA3 has been included in GtoImmuPdb as its expression has been detected in immune cells [19] ...
                CXCR3
                (Chemokine receptors)
                • T-helper 1 cell (CL:0000545)
                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.
                S1P1 receptor
                (Lysophospholipid (S1P) receptors)
                B- and T-lymphocytes predominantly express S1P1 receptors, with S1P3 and S1P4 expressed at lower levels.
                • alpha-beta T cell (CL:0000789)
                S1P1R activation by agonists downregulates allergic inflammation (i.e. it has an inhibitory effect) [38-39,73] ...
                Ion Channels
                GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
                Kv1.3
                (Voltage-gated potassium channels)
                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 pharmacologocal manipulation of Kv1.3 activity may be of clinical utility in immunomodualtion [1,13,21,32] ...
                  TRPC3
                  (Transient Receptor Potential channels)
                  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 [67] ...
                    TRPC5
                    (Transient Receptor Potential channels)
                    TRPC5 (along with TRPC3 and TRPC6) is involved in TCR signalling, proliferation and autoimmune suppression.
                      Expressed on mouse T cells [67] ...
                      Enzymes
                      GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
                      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 [66] ...
                        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) [66] ...
                          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 [15] ...
                            phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
                            (Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
                            • alpha-beta T cell (CL:0000789)
                            The potential for PI3kδ as ta arget in immuno-oncology is discussed in [2] ...
                            cathepsin C
                            (C1: Papain)
                            • mature CD8 single-positive thymocyte (CL:0002437)
                            Cathepsin C is a lysosomal cysteine protease constitutively expressed at high levels in lung, kidney, liver and spleen. As well as activity in lysosomal protein degradation, catheposin C also plays a key role in the activation of granule serine proteases in cytotoxic T cells, natural killer cells (g ...
                            phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
                            (Phosphatidylinositol-4,5-bisphosphate 3-kinase family)
                            • alpha-beta T cell (CL:0000789)
                            The potential for PI3kδ as ta arget in immuno-oncology is discussed in [2] ...
                            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.
                            • CD4-positive helper T cell (CL:0000492)
                            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 and graft versus host disease (GvHD) [41] ...
                            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)
                            • mature NK T cell (CL:0000814)
                            Mer plays a critical role in regulating self-tolerance mediated between apoptotic cells, dendritic cells, and T cells [14,87] ...
                            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 [77].
                              • effector T cell (CL:0000911)
                              This is the ligand binding subunit of the functional IL-7 receptor complex.
                              Other Protein Targets
                              GtoPdb receptor name (family) Cell Type Association Comments Cell Ontology Associations Immunopharmacology Comments
                              TIGIT
                              (Immunoglobulins)
                              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 ...
                                CD80
                                (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 ...
                                  CD28
                                  (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 [5] ...
                                    LAG3 (CD223)
                                    (CD molecules)
                                    LAG3 is an activation marker for CD4+ and CD8+ T cells.
                                    • CD4-positive, alpha-beta T cell (CL:0000624)
                                    • CD8-positive, alpha-beta T cell (CL:0000625)
                                    LAG3 (CD223) is a T cell inhibitory receptor and immune checkpoint being investigated as a cancer immunotherapeutic target [7] ...
                                    programmed cell death 1 (CD279)
                                    (CD molecules)
                                    PD-1 expression is induced in murine T cells activated by stimulation through antigen receptors.
                                    • activated CD4-positive, alpha-beta T cell (CL:0000896)
                                    • activated CD8-positive, alpha-beta T cell (CL:0000906)
                                    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 [65] ...
                                    TIM3 (CD366)
                                    (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.
                                    • T-helper 1 cell (CL:0000545)
                                    TIM3 is an immunoglobulin type protein expressed exclusively on the surface of differentiated Th1 cells [57] ...
                                    TIGIT
                                    (Immunoglobulins)
                                    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 ...
                                      CD3e
                                      (CD molecules)
                                        CD3e is part of the CD3/TCR complex that mediates T-cell receptor signal transduction. Defects in this gene cause severe immunodeficiency [28,78] ...
                                        CD2
                                        (CD molecules)
                                          CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells [88] ...
                                          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 [59] ...
                                            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) [44] ...
                                              CD28
                                              (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 [5] ...
                                                regulator of G-protein signaling 1
                                                (R4 family)
                                                • T follicular helper cell (CL:0002038)
                                                RGS1 is expresses in lymphocytes and macrophages and plays a role in leukocyte trafficking and vascular inflammation [18,36,58,68] ...
                                                CD38
                                                (CD molecules)
                                                  CD38 is a type II transmembrane glycoprotein, widely expressed on immune cells and 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 [35] ...
                                                  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)
                                                    • B cell (CL:0000236)
                                                    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 [25] ...
                                                    CD80
                                                    (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 ...
                                                      LAG3 (CD223)
                                                      (CD molecules)
                                                      LAG3 is an activation marker for CD4+ and CD8+ T cells.
                                                      • CD4-positive, alpha-beta T cell (CL:0000624)
                                                      • CD8-positive, alpha-beta T cell (CL:0000625)
                                                      LAG3 (CD223) is a T cell inhibitory receptor and immune checkpoint being investigated as a cancer immunotherapeutic target [7] ...
                                                      programmed cell death 1 (CD279)
                                                      (CD molecules)
                                                      PD-1 expression is induced in murine T cells activated by stimulation through antigen receptors.
                                                      • activated CD4-positive, alpha-beta T cell (CL:0000896)
                                                      • activated CD8-positive, alpha-beta T cell (CL:0000906)
                                                      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 [65] ...
                                                      CD300a
                                                      (CD molecules)
                                                      • CD4-positive, alpha-beta T cell (CL:0000624)
                                                      • T-helper 1 cell (CL:0000545)
                                                      CD300a is a member of the CD300 family of leucocyte surface receptors [17] ...
                                                      TIM3 (CD366)
                                                      (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.
                                                      • T-helper 1 cell (CL:0000545)
                                                      TIM3 is an immunoglobulin type protein expressed exclusively on the surface of differentiated Th1 cells [57] ...