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CTLA4
CTLA-4 or CTLA4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152 (cluster of differentiation 152), is a protein receptor that functions as an immune checkpoint and downregulates immune responses. 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. The CTLA-4 protein is encoded by the ''Ctla-4'' gene in mice and the ''CTLA-4'' gene in humans. 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 H. 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 not defi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CD28
CD28 (Cluster of Differentiation 28) is one of the proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and survival. T cell stimulation through CD28 in addition to the T-cell receptor ( TCR) can provide a potent signal for the production of various interleukins ( IL-6 in particular). CD28 is the receptor for CD80 (B7.1) and CD86 (B7.2) proteins. When activated by Toll-like receptor ligands, the CD80 expression is upregulated in antigen-presenting cells (APCs). The CD86 expression on antigen-presenting cells is constitutive (expression is independent of environmental factors). CD28 is the only B7 receptor constitutively expressed on naive T cells. Association of the TCR of a naive T cell with MHC:antigen complex without CD28:B7 interaction results in a T cell that is anergic. Furthermore, CD28 was also identified on bone marrow stromal cells, plasma cells, neutrophils and eosinophils, but the functional importance of CD28 on these ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immune Checkpoint
Immune checkpoints are regulators of the immune system. These pathways are crucial for self-tolerance, which prevents the immune system from attacking cells indiscriminately. However, some cancers can protect themselves from attack by stimulating immune checkpoint targets. Inhibitory checkpoint molecules are targets for cancer immunotherapy due to their potential for use in multiple types of cancers. Currently approved checkpoint inhibitors block CTLA4 and PD-1 and PD-L1. For the related basic science discoveries, James P. Allison and Tasuku Honjo won the Tang Prize in Biopharmaceutical Science and the Nobel Prize in Physiology or Medicine in 2018. Stimulatory checkpoint molecules Four stimulatory checkpoint molecules are members of the tumor necrosis factor (TNF) receptor superfamily—CD27, CD40, OX40, GITR and CD137. Another two stimulatory checkpoint molecules belong to the B7-CD28 superfamily—CD28 itself and ICOS. * CD27: This molecule supports antigen-specific ex ... [...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 ligand ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Regulatory T Cell
The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells. Treg cells express the biomarkers CD4, FOXP3, and CD25 and are thought to be derived from the same lineage as naïve CD4+ cells. Because effector T cells also express CD4 and CD25, Treg cells are very difficult to effectively discern from effector CD4+, making them difficult to study. Research has found that the cytokine transforming growth factor beta (TGF-β) is essential for Treg cells to differentiate from naïve CD4+ cells and is important in maintaining Treg cell homeostasis. Mouse models have suggested that modulation of Treg cells can treat autoimmune disease and cancer and can facilitate orga ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Regulatory T Cells
The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosuppressive and generally suppress or downregulate induction and proliferation of effector T cells. Treg cells express the biomarkers CD4, FOXP3, and CD25 and are thought to be derived from the same lineage as naïve CD4+ cells. Because effector T cells also express CD4 and CD25, Treg cells are very difficult to effectively discern from effector CD4+, making them difficult to study. Research has found that the cytokine transforming growth factor beta (TGF-β) is essential for Treg cells to differentiate from naïve CD4+ cells and is important in maintaining Treg cell homeostasis. Mouse models have suggested that modulation of Treg cells can treat autoimmune disease and cancer and can facilitate orga ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immunoglobulin V-set Domain
V-set domains are Ig-like domains resembling the antibody variable domain. V-set domains are found in diverse protein families, including immunoglobulin light and heavy chains; in several T-cell receptors such as CD2 (Cluster of Differentiation 2), CD4, CD80, and CD86; in myelin membrane adhesion molecules; in junctional adhesion molecules (JAM); in tyrosine-protein kinase receptors; and in the programmed cell death protein 1 (PD1). Subfamilies * Immunoglobulin V-set, subgroup * T-cell surface antigen CD2 Human proteins containing this domain ACAM; ACAN; ADAMTSL1; AGC1; AMICA1; BCAM; BCAN; BGP; BGPc; BT3.3; BTN1A1; BTN2A1; BTN2A2; BTN2A3; BTN3A1; BTN3A2; BTN3A3; BTNL2; BTNL3; BTNL8; BTNL9; C10orf54; C1orf32; C9orf94; CADM1; CADM2; CADM3; CADM4; CD2; CD226; CD274; CD276; CD300A; CD300C; CD300D; CD300E; CD300LB; CD300LF; CD300LG; ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cluster Of Differentiation
The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophenotyping of cells. In terms of physiology, CD molecules can act in numerous ways, often acting as receptors or ligands important to the cell. A signal cascade is usually initiated, altering the behavior of the cell (see cell signaling). Some CD proteins do not play a role in cell signaling, but have other functions, such as cell adhesion. CD for humans is numbered up to 371 (). Nomenclature The CD nomenclature was proposed and established in the 1st International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA), which was held in Paris in 1982. This system was intended for the classification of the many monoclonal antibodies (mAbs) generated by different laboratories around the world against epitopes on the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Homodimer
In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has roots meaning "two parts", '' di-'' + '' -mer''. A protein dimer is a type of protein quaternary structure. A protein homodimer is formed by two identical proteins. A protein heterodimer is formed by two different proteins. Most protein dimers in biochemistry are not connected by covalent bonds. An example of a non-covalent heterodimer is the enzyme reverse transcriptase, which is composed of two different amino acid chains. An exception is dimers that are linked by disulfide bridges such as the homodimeric protein NEMO. Some proteins contain specialized domains to ensure dimerization (dimerization domains) and specificity. The G protein-coupled cannabinoid receptors have the ability to form both homo- and heterodimers with several ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alternative Splicing
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final, processed messenger RNA (mRNA) produced from that gene. This means the exons are joined in different combinations, leading to different (alternative) mRNA strands. Consequently, the proteins translated from alternatively spliced mRNAs will contain differences in their amino acid sequence and, often, in their biological functions (see Figure). Biologically relevant alternative splicing occurs as a normal phenomenon in eukaryotes, where it increases the number of proteins that can be encoded by the genome. In humans, it is widely believed that ~95% of multi-exonic genes are alternatively spliced to produce functional alternative products from the same gene but many scientists believe that most o ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein Isoform
A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have unique functions. A set of protein isoforms may be formed from alternative splicings, variable promoter usage, or other post-transcriptional modifications of a single gene; post-translational modifications are generally not considered. (For that, see Proteoforms.) Through RNA splicing mechanisms, mRNA has the ability to select different protein-coding segments ( exons) of a gene, or even different parts of exons from RNA to form different mRNA sequences. Each unique sequence produces a specific form of a protein. The discovery of isoforms could explain the discrepancy between the small number of protein coding regions genes revealed by the human genome project and the large diversity of proteins seen in an organism: different ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein Phosphatase 2
Protein phosphatase 2 (PP2), also known as PP2A, is an enzyme that in humans is encoded by the ''PPP2CA'' gene. The PP2A heterotrimeric protein phosphatase is ubiquitously expressed, accounting for a large fraction of phosphatase activity in eukaryotic cells. Its serine/threonine phosphatase activity has a broad substrate specificity and diverse cellular functions. Among the targets of PP2A are proteins of oncogenic signaling cascades, such as Raf, MEK, and AKT, where PP2A may act as a tumor suppressor. Structure and function PP2A consists of a dimeric core enzyme composed of the structural A and catalytic C subunits, and a regulatory B subunit. When the PP2A catalytic C subunit associates with the A and B subunits several species of holoenzymes are produced with distinct functions and characteristics. The A subunit, a founding member of the HEAT repeat protein family (huntington-elongation-A subunit-TOR), is the scaffold required for the formation of the heterotrimeric co ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Disulfide Bond
In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In biology, disulfide bridges formed between thiol groups in two cysteine residues are an important component of the secondary and tertiary structure of proteins. ''Persulfide'' usually refers to compounds. In inorganic chemistry disulfide usually refers to the corresponding anion (−S−S−). Organic disulfides Symmetrical disulfides are compounds of the formula . Most disulfides encountered in organo sulfur chemistry are symmetrical disulfides. Unsymmetrical disulfides (also called heterodisulfides) are compounds of the formula . They are less common in organic chemistry, but most disulfides in nature are unsymmetrical. Properties The disulfide bonds are strong, with a typical bond dissociation energy of 60 kcal/mol (251& ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
