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 (as of 21 April 2016 ).
27-504: CD1 ( cluster of differentiation 1) is a family of glycoproteins expressed on the surface of various human antigen-presenting cells . CD1 glycoproteins are structurally related to the class I MHC molecules, however, in contrast to MHC class 1 proteins , they present lipids , glycolipids and small molecules antigens, from both endogenous and pathogenic proteins, to T cells and activate an immune response. Both αβ and γδ T cells recognise CD1 molecules. The human CD1 gene cluster
54-410: A chemokine receptor on the surface of a T helper cell to gain entry. The number of CD4 and CD8 T cells in blood is often used to monitor the progression of HIV infection . While CD molecules are very useful in defining leukocytes, they are not merely markers on the cell surface . Though only a fraction of known CD molecules have been thoroughly characterised, most of them have important functions. In
81-578: A stem cell , as opposed to a fully differentiated endothelial cell . Some cell populations can also be defined as , , or (alternatively, , , or ), indicating an overall variability in CD expression , particularly when compared to other cells being studied. A review of the development of T cells in the thymus uses this nomenclature to identify cells transitioning from CD4 /CD8 double-positive cells to CD4 /CD8 . Since 1982 there have been nine Human Leukocyte Differentiation Antigen Workshops culminating in
108-428: A class of amphiphilic molecules, are the main components of biological membranes . The amphiphilic nature of these molecules defines the way in which they form membranes. They arrange themselves into lipid bilayers , by forming a sheet composed of two layers of lipids. Each layer forms by positioning their lypophilic chains to the same side of the layer. The two layers then stack such that their lyphphilic chains touch on
135-426: A conference. The CD system is commonly used as cell markers in immunophenotyping , allowing cells to be defined based on what molecules are present on their surface. These markers are often used to associate cells with certain immune functions . While using one CD molecule to define populations is uncommon (though a few examples exist), combining markers has allowed for cell types with very specific definitions within
162-452: A pathogen in humans as well, it is hoped that studying cows will yield insights into the group 1 CD1 antigen-presenting system. Cluster of differentiation The CD nomenclature was proposed and established in the 1st International Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA), held in Paris in 1982. This system was intended for the classification of
189-424: A result of having both lipophilic and hydrophilic portions, some amphiphilic compounds may dissolve in water and to some extent in non-polar organic solvents . When placed in an immiscible biphasic system consisting of aqueous and organic solvents, the amphiphilic compound will partition the two phases. The extent of the hydrophobic and hydrophilic portions determines the extent of partitioning. Phospholipids ,
216-524: A synthetic glycolipid, alpha-galactosylceramide (α-GalCer), originally isolated from a compound found in a marine sponge , has strong biologic activity. Group 2 CD1 molecules activate a group of T cells, known as Natural killer T cells because of their expression of NK surface markers such as CD161 . Natural Killer T (NKT) cells are activated by CD1d-presented antigens, and rapidly produce Th1 and Th2 cytokines, typically represented by interferon-gamma and IL-4 production. The group 2 (CD1d) ligand α-GalCer
243-539: Is a chemical compound possessing both hydrophilic ( water-loving , polar ) and lipophilic ( fat-loving , nonpolar) properties. Such a compound is called amphiphilic or amphipathic . Amphiphilic compounds include surfactants and detergents . The phospholipid amphiphiles are the major structural component of cell membranes . Amphiphiles are the basis for a number of areas of research in chemistry and biochemistry, notably that of lipid polymorphism . Organic compounds containing hydrophilic groups at both ends of
270-475: Is an intermediate form, a soluble lipid transfer protein that is expressed intracellularly. It does not present lipid antigens to T cells, rather plays a role in the processing of lipid antigens and loading them onto other CD1 molecules. Group 1 CD1 molecules have been shown to present foreign lipid antigens, and specifically a number of mycobacterial cell wall components, to CD1-specific T cells. The natural antigens of group 2 CD1 are not well characterized, but
297-673: Is currently in phase I clinical trials for the treatment of advanced non-hematologic cancers. CD1 proteins consist of a heavy chain with α1, α2, and α3 domains and a transmembrane domain which anchors it to the cell membrane. Much like the MHC molecules, the CD1 heavy chain associates with β2-microglobulin and its binding groove consists of two antiparallel α-helices , placed atop a β-sheet platform. The antigen-binding cleft architecture of CD1 proteins consists of A’, C’, F’ and T’ binding pockets and C’ and D’/E’ accessory portals, which act to accommodate
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#1732765993393324-453: Is located on chromosome 1 . Genes of the CD1 family were first cloned in 1986, by Franco Calabi and C. Milstein, whereas the first known lipid antigen for CD1 was discovered in 1994, during studies of Mycobacterium tuberculosis . The first antigen that was discovered to be able to bind CD1 and then be recognised by TCR is C80 mycolic acid . Even though their precise function is unknown, The CD1 system of lipid antigen recognition by TCR offers
351-597: Is that the antigen display platform of CD1 molecules is smaller than the antigen display groove of MHC molecules. Human CD1 cells can recognise and bind a large number of lipids, from monoacylated lipids or lipopeptides to tetra-acylated lipids. However, not all of the lipid ligands can be considered antigens for T-cells. Free fatty acids sphingolipids , phospholipids, sulfolipids , lysophospholipids, amphipathic small molecules and some oils function as natural antigens for T cells. 10% of all αβ T lymphocytes in human peripheral blood are CD1-restricted T cells , out of which,
378-451: The aliphatic hydrocarbon chains present in lipid, glycolipid , phospholipid , or lipopeptide antigens. CD1 antigen binding clefts are defined by locations of named portals where antigens protrude. The main difference in structure between MHC and CD1 proteins is that in MHC proteins, the contact region for TCR show lateral symmetry, whereas human CD1 proteins show left-right asymmetry . Another difference between MHC and CD1 proteins
405-1006: The description of the small (40,42 aa) plaque-forming (aggregative) Aβ fragments. Antimicrobial peptides (AMPs) are another class of amphiphilic molecules, a big data analysis showed that amphipathicity best distinguished between AMPs with and without anti-gram-negative bacteria activities. The higher amphipathicity, the better chances for AMPs possessing antibacterial and antifungal dual activities. There are several examples of molecules that present amphiphilic properties: Hydrocarbon -based surfactants are an example group of amphiphilic compounds. Their polar region can be either ionic , or non-ionic. Some typical members of this group are: sodium dodecyl sulfate ( anionic ), benzalkonium chloride ( cationic ), cocamidopropyl betaine ( zwitterionic ), and 1-octanol (long-chain alcohol, non-ionic). Many biological compounds are amphiphilic: phospholipids , cholesterol , glycolipids , fatty acids , bile acids , saponins , local anaesthetics, etc. Soap
432-426: The designation (e.g., CD2 molecule). Currently, "CD2" is generally used to designate the molecule, and "CD2 antibody " is used to designate the antibody. Cell populations are usually defined using a '+' or a '−' symbol to indicate whether a certain cell fraction expresses or lacks a CD molecule. For example, a " CD34 +, CD31 −" cell is one that expresses CD34 but not CD31. This CD combination typically corresponds to
459-563: The example of CD4 and CD8, these molecules are critical in antigen recognition. Others (e.g., CD135 ) act as cell surface receptors for growth factors . Recently, the marker CD47 was found to have anti- phagocytic signals to macrophages and inhibit natural killer (NK) cells. This enabled researchers to apply CD47 as a potential target to attenuate immune rejection . Amphiphile In chemistry , an amphiphile (from Greek αμφις (amphis) 'both' and φιλíα ( philia ) 'love, friendship'), or amphipath ,
486-405: The group 1 CD1 molecules, and instead have 2 copies of CD1d . Thus, mice have been used extensively to characterize the role of CD1d and CD1d-dependent NKT cells in a variety of disease models. It has recently been shown that cows lack the group 2 CD1 molecules, and have an expanded set of group 1 CD1 molecules. Because of this and the fact that cows are a natural host of Mycobacterium bovis ,
513-432: The hydrophobic part into the lipid membrane, while exposing the hydrophilic part to the aqueous medium, altering their physical behavior and sometimes disrupting them. Aβ proteins form antiparallel β sheets which are strongly amphiphilic, and which aggregate to form toxic oxidative Aβ fibrils. Aβ fibrils themselves are composed of amphiphilic 13-mer modular β sandwiches separated by reverse turns. Hydropathic waves optimize
540-509: The immune system. CD molecules are utilized in cell sorting using various methods, including flow cytometry . Two commonly used CD molecules are CD4 and CD8 , which are, in general, used as markers for helper and cytotoxic T cells, respectively. These molecules are defined in combination with CD3+, as some other leukocytes also express these CD molecules (some macrophages express low levels of CD4; dendritic cells express high levels of CD8). Human immunodeficiency virus binds CD4 and
567-561: The inside and their polar groups are outside facing the surrounding aqueous media. Thus the inside of the bilayer sheet is a non-polar region sandwiched between the two polar sheets. Although phospholipids are the principal constituents of biological membranes, there are other constituents, such as cholesterol and glycolipids , which are also included in these structures and give them different physical and biological properties. Many other amphiphilic compounds, such as pepducins , strongly interact with biological membranes by insertion of
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#1732765993393594-422: The many monoclonal antibodies (mAbs) generated by different laboratories around the world against epitopes on the surface molecules of leukocytes (white blood cells). Since then, its use has expanded to many other cell types, and more than 370 CD unique clusters and subclusters have been identified. The proposed surface molecule is assigned a CD number once two specific monoclonal antibodies are shown to bind to
621-629: The molecule are called bolaamphiphilic . The micelles they form in the aggregate are prolate . The lipophilic group is typically a large hydrocarbon moiety , such as a long chain of the form CH 3 (CH 2 ) n , with n > 4. The hydrophilic group falls into one of the following categories: Often, amphiphilic species have several lipophilic parts, several hydrophilic parts, or several of both. Proteins and some block copolymers are such examples. Amphiphilic compounds have lipophilic (typically hydrocarbon ) structures and hydrophilic polar functional groups (either ionic or uncharged). As
648-409: The molecule. If the molecule has not been well characterized or has only one mAb, it is usually given the provisional indicator "w" (as in " CDw186 "). For instance, CD2 mAbs are reagents that react with a 50‐kDa transmembrane glycoprotein expressed on T cells . The CD designations were used to describe the recognized molecules but had to be clarified by attaching the term antigen or molecule to
675-585: The most abundant are the T cells specific for CD1c. Three models of CD1 recognition by TCR have been described: “head group recognition” model, “absence of interference” model and “altered CD1” model. The “head group recognition” model is considered to be a classical mode of CD1-antigen recognition, whereas the other two are only “emerging” CD1-antigen recognition models which predict that TCR contacts CD1 and not lipid. CD1 antigens are expressed on cortical thymocytes , but not on mature T cells. This often remains true in neoplastic cells from these populations, so that
702-421: The presence of CD1 antigens can be used in diagnostic immunohistochemistry to identify some thymomas and malignancies arising from T cell precursors. CD1a, in particular, is a specific marker for Langerhans cells , and can therefore also be used in the diagnosis of Langerhans cell histiocytosis . Other conditions that may show CD1 positivity include myeloid leukaemia and some B cell lymphomas . Mice lack
729-403: The prospect of discovering new approaches to therapy and developing immunomodulatory agents. CD1 glycoproteins can be classified primarily into two groups of CD1 isoforms which differ in their lipid anchoring, as well as their expression patterns of the CD1 genes (CD1d is constitutively expressed, whereas the group 1 CD1 genes are inducible and coordinately regulated by myeloid cells ). CD1e
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