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Costimulation
Co-stimulation is a secondary signal which immune cells rely on to activate an immune response in the presence of an antigen-presenting cell. In the case of T cells, two stimuli are required to fully activate their immune response. During the activation of lymphocytes, co-stimulation is often crucial to the development of an effective immune response. Co-stimulation is required in addition to the antigen-specific signal from their antigen receptors. T cell co-stimulation T cells require two signals to become fully activated. A first signal, which is antigen-specific, is provided through the T cell receptor (TCR) which interacts with peptide- MHC molecules on the membrane of an antigen presenting cell (APC). A second signal, the co-stimulatory signal, is antigen nonspecific and is provided by the interaction between co-stimulatory molecules expressed on the membrane of the APC and the T cell. This interaction promotes and enhances the TCR signaling, but can also be bi-directional. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CD28 Family Receptor
CD28 family receptors are a group of regulatory cell surface receptors expressed on immune cells. The CD28 family in turn is a subgroup of the immunoglobulin superfamily. Two family members, CD28 and ICOS, act as positive regulators of T cell function while another three, BTLA, CTLA-4 and PD-1 act as inhibitors. Ligands for the CD28 receptor family include B7 family proteins. CD28 receptors play a role in the development and proliferation of T cells. The CD28 receptors enhance signals from the T cell receptors (TCR) in order to stimulate an immune response and an anti-inflammatory response on regulatory T cells. Through the promotion of T cell function, CD28 receptors allow effector T cells to combat regulatory T cell-mediated suppression from adaptive immunity. CD28 receptors also elicit the prevention of spontaneous autoimmunity. Function CD28 receptors aid in other T cell processes such as cytoskeletal remodeling, production of cytokines and chemokines and intracellul ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CD28
CD28 (Cluster of Differentiation 28) is a protein expressed on T cells that provides essential co-stimulation, co-stimulatory signals required for T cell activation and survival. When T cells are stimulated through CD28 in conjunction with the T-cell receptor (T cell receptor, TCR), it enhances the production of various interleukins, particularly interleukin 6, IL-6. CD28 serves as a receptor for CD80 (B7.1) and CD86 (B7.2), proteins found on antigen-presenting cells (APCs). CD28 is the only B7 (protein), B7 receptor consistently expressed on naive T cells. In the absence of CD28:B7 interaction, a naive T cell's TCR engagement with an Major histocompatibility complex, MHC:antigen complex leads to anergy. CD28 is also expressed on bone marrow stromal cells, plasma cells, neutrophils, and eosinophils, although its function in these cells is not fully understood. Typically, CD28 is expressed on about 50% of CD8, CD8+ T cells and more than 80% of CD4, CD4+ T cells in humans. However, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ICOSLG
ICOS ligand is a protein that in humans is encoded by the ''ICOSLG'' gene located at chromosome 21. ICOSLG has also been designated as CD275 (cluster of differentiation 275). ICOSLG is glycosylated transmembrane structure, which is classified as a member of the B7 family due to the significant homology with B7 family members. The B7/CD28 superfamily provides both positive and negative co-signals to immunocytes in immune responses. The interaction of ICOSLG with ICOS, the specific receptor for ICOSLG, is critically involved in the activation, proliferation, differentiation and cytokine production of T cells as well as in the antibody secretion from B cells during secondary immune responses. ICOSLG, which is extensively expressed in both non-lymphatic and lymphatic tissues, is an important molecule in upregulating and promoting T cell immune responses. Expression of ICOSLG in naive B cells and monocytes in PBMCs is at a low level. After stimulation by IFN-γ, TNF-α, or LPS, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CD134
Tumor necrosis factor receptor superfamily, member 4 (TNFRSF4), also known as CD134 and OX40 receptor, is a member of the TNFR-superfamily of receptors which is not constitutively expressed on resting naïve T cells, unlike CD28. OX40 is a secondary co-stimulatory immune checkpoint molecule, expressed after 24 to 72 hours following activation; its ligand, OX40L, is also not expressed on resting antigen presenting cells, but is following their activation. Expression of OX40 is dependent on full activation of the T cell; without CD28, expression of OX40 is delayed and of fourfold lower levels. Function OX40 has no effect on the proliferative abilities of CD4+ cells for the first three days, however after this time proliferation begins to slow and cells die at a greater rate, due to an inability to maintain a high level of PKB activity and expression of Bcl-2, Bcl-XL and survivin. OX40L binds to OX40 receptors on T-cells, preventing them from dying and subsequently increasi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CD80
The Cluster of differentiation 80 (also CD80 and B7-1) is a B7, type I membrane protein in the immunoglobulin superfamily, with an extracellular immunoglobulin constant-like domain and a variable-like domain required for receptor binding. It is closely related to CD86, another B7 protein (B7-2), and often works in tandem. Both CD80 and CD86 interact with Co-stimulation, costimulatory receptors CD28, CTLA-4 (CD152) and the p75 neurotrophin receptor. Structure CD80 is a member of the B7 (protein), B7 family, which consists of molecules present at Antigen-presenting cell, APCs and their receptors present on the T cell, T-cells. CD80 is present specifically on Dendritic cell, DC, activated B cell, B-cells, and macrophages, but also T cell, T-cells. CD80 is also a Transmembrane protein, transmembrane glycoprotein and a member of the Immunoglobulin superfamily, Ig superfamily. It is composed of 288 amino acids, and its mass is 33 Dalton (unit), kDa. It consists of two Ig-like extracel ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CD278
Inducible T-cell costimulator (also called CD278) is an immune checkpoint protein that in humans is encoded by the ''ICOS'' (Inducible T-cell COStimulator) gene. The protein belongs to the CD28 and Cytotoxic T-lymphocyte associated protein 4, CTLA-4 cell-surface receptor family. These are proteins expressed on the surface of immune cells that mediate signalling between them. A surface protein, the ligand, binds specifically to its receptor on another cell, leading to a signalling cascade in that cell. Function ICOS is a receptor protein expressed on the surface of activated T cells. Its ligand ICOSLG, ICOS-L (previously called B7RP-1) is constitutively expressed on B cells. Stimulation of the ICOS receptor on T cells by ICOS-L on B cells is required for the development of Follicular B helper T cells, follicular helper T (Tfh) cells. ICOS forms Protein dimer, homodimers and plays an important role in cell-cell signaling, immune responses and regulation of cell proliferation. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immune Tolerance
Immune tolerance, also known as immunological tolerance or immunotolerance, refers to the immune system's state of unresponsiveness to substances or tissues that would otherwise trigger an immune response. It arises from prior exposure to a specific antigen and contrasts the immune system's conventional role in eliminating foreign antigens. Depending on the site of induction, tolerance is categorized as either central tolerance, occurring in the thymus and bone marrow, or peripheral tolerance, taking place in other tissues and lymph nodes. Although the mechanisms establishing central and peripheral tolerance differ, their outcomes are analogous, ensuring immune system modulation. Immune tolerance is important for normal physiology and homeostasis. Central tolerance is crucial for enabling the immune system to differentiate between self and non-self antigens, thereby preventing autoimmunity. Peripheral tolerance plays a significant role in preventing excessive immune reactions to en ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CD226
CD226 (Cluster of Differentiation 226), PTA1 (outdated term, 'platelet and T cell activation antigen 1') or DNAM-1 ( DNAX Accessory Molecule-1) is a ''~65 kDa'' immunoglobulin-like transmembrane glycoprotein expressed on the surface of natural killer cells, NK T cell, B cells, dendritic cells, hematopoietic precursor cells, platelets, monocytes and T cells. DNAM-1 gene ''CD226'' is conserved between human and mice. In humans the CD226 gene is located on chromosome 18q22.3. In mice the CD226 gene is located on chromosome 18E4. Structure DNAM-1 is composed of three domains: an extracellular domain of 230 amino acids with two immunoglobin-like V-set domains and eight N-glycosylation sites, a transmembrane domain of 28 amino acids and a cytosolic domain of 60 amino acids containing four putative tyrosine residues and one serine residue for phosphorylation. Signaling Upon engagement to its ligand, DNAM-1 is phosphorylated by protein kinase C. Then adhesive molecule LFA-1 cros ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CTLA-4
Cytotoxic T-lymphocyte associated protein 4, (CTLA-4) also known as CD152 ( cluster of differentiation 152), is a protein receptor that functions as an immune checkpoint and downregulates immune responses. CTLA-4 is constitutively expressed in regulatory T cells but only upregulated in conventional T cells after activation – a phenomenon which is particularly notable in cancers. It acts as an "off" switch when bound to CD80 or CD86 on the surface of antigen-presenting cells. It is encoded by the gene ''CTLA4'' in humans. The CTLA-4 protein is encoded by the ''Ctla-4'' gene in mice. History CTLA-4 was first identified in 1991 as a second receptor for the T cell costimulation ligand B7. In November 1995, the labs of Tak Wah Mak and Arlene Sharpe independently published their findings on the discovery of the function of CTLA-4 as a negative regulator of T-cell activation, by knocking out the gene in mice. Previous studies from several labs had used methods which could ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CD137
CD137, a member of the tumor necrosis factor ( TNF) receptor family, is a type 1 transmembrane protein, expressed on surfaces of leukocytes and non-immune cells. Its alternative names are ''tumor necrosis factor receptor superfamily member 9'' (TNFRSF9), 4-1BB, and ''induced by lymphocyte activation'' (ILA). It is of interest to immunologists as a co-stimulatory immune checkpoint molecule, and as a potential target in cancer immunotherapy. Expression CD137 is only expressed on the T-cell cell surface after activation. When T cells are activated by Antigen Presenting Cells (APCs), CD137 becomes embedded in CD4+ and CD8+ T cells. CD137 is a costimulatory molecule functioning to stimulate T cell proliferation, dendritic cell maturation, and promotion of B cell antibody secretion. As a T cell co-stimulator, T cell receptor (TCR) and CD28 signaling causes expression of CD137 on T cell membranes. When CD137 then reacts with the CD137 ligand, it leads to CD137 upregulation. This is a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CD86
Cluster of Differentiation 86 (also known as CD86 and B7-2) is a protein constitutively expressed on dendritic cells, Langerhans cells, macrophages, B-cells (including memory B-cells), and on other antigen-presenting cells. Along with CD80, CD86 provides costimulatory signals necessary for T cell activation and survival. Depending on the ligand bound, CD86 can signal for self-regulation and cell-cell association, or for attenuation of regulation and cell-cell disassociation. The ''CD86'' gene encodes a type I membrane protein that is a member of the immunoglobulin superfamily. Alternative splicing results in two transcript variants encoding different isoforms. Additional transcript variants have been described, but their full-length sequences have not been determined. Structure CD86 belongs to the B7 family of the immunoglobulin superfamily. It is a 70 kDa glycoprotein made up of 329 amino acids. Both CD80 and CD86 share a conserved amino acid motif that forms their l ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immunological Synapse
In immunology, an immunological synapse (or immune synapse) is the interface between an antigen-presenting cell or target cell and a lymphocyte such as a T cell, B cell, or natural killer cell. The interface was originally named after the neuronal synapse, with which it shares the main structural pattern. An immunological synapse consists of molecules involved in T cell activation, which compose typical patterns—activation clusters. Immunological synapses are the subject of much ongoing research. Structure and function The immune synapse is also known as the supramolecular activation cluster or SMAC. This structure is composed of concentric rings each containing segregated clusters of proteins—often referred to as the bull’s-eye model of the immunological synapse: * c-SMAC (central-SMAC) composed of the θ isoform of protein kinase C, CD2, CD4, CD8, CD28, Lck, and Fyn. * p-SMAC (peripheral-SMAC) within which the lymphocyte function-associated antigen-1 ( LFA-1) and the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
