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 molecule Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...

s providing targets for immunophenotyping of cells. In terms of physiology, CD molecules can act in numerous ways, often acting as

receptors Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...

or ligands important to the cell. A signal cascade is usually initiated, altering the behavior of the cell (see

cell signaling In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...

). 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

Antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...

s (HLDA), which was held in

Paris Paris () is the Capital city, capital and List of communes in France with over 20,000 inhabitants, most populous city of France, with an estimated population of 2,165,423 residents in 2019 in an area of more than 105 km² (41 sq mi), ma ...

in 1982. This system was intended for the classification of the many monoclonal antibodies (mAbs) generated by different laboratories around the world against

epitope An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The epitope is the specific piece of the antigen to which an antibody binds. The p ...

s 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 (mAb) are shown to bind to 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 the designation (e.g., CD2 molecule). Currently, "

CD2 CD2 (cluster of differentiation 2) is a cell adhesion molecule found on the surface of T cells and natural killer (NK) cells. It has also been called T-cell surface antigen T11/Leu-5, LFA-2, LFA-3 receptor, erythrocyte receptor and rosette rece ...

" 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 CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species. CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first descri ...

CD31 Platelet endothelial cell adhesion molecule (PECAM-1) also known as cluster of differentiation 31 (CD31) is a protein that in humans is encoded by the ''PECAM1'' gene found on chromosome17q23.3. PECAM-1 plays a key role in removing aged neutrop ...

−" cell is one that expresses CD34, but not CD31. This CD combination typically corresponds to a stem cell, as opposed to a fully differentiated endothelial cell. Some cell populations can also be defined as ^hi, ^mid or ^low(alternatively ^bright, ^mid or ^dim), 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 The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. ...

uses this nomenclature to identify cells transitioning from CD4^mid/CD8^mid double positive cells to CD4^hi/CD8^mid.

Human Leukocyte Differentiation Antigen Workshops

Since 1982 there have been nine Human Leukocyte Differentiation Antigen Workshops culminating in a conference.

Immunophenotyping

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 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 CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). Along with the TCR, the CD8 co-receptor plays a role in T cell signaling and aiding with cytotoxic T cell-antigen int ...

, 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 Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. The ...

express high levels of CD8). Human immunodeficiency virus (HIV) binds CD4 and 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.

Physiological functions

While CD molecules are very useful in defining leukocytes, they are not merely markers on the cell surface. While only a fraction of known CD molecules have been thoroughly characterised, most of them have an important function. In the example of CD4 & CD8, these molecules are critical in

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...

recognition. Others (e.g.,

CD135 Cluster of differentiation antigen 135 (CD135) also known as fms like tyrosine kinase 3 (FLT-3), receptor-type tyrosine-protein kinase FLT3, or fetal liver kinase-2 (Flk2) is a protein that in humans is encoded by the ''FLT3'' gene. FLT3 is a cyto ...

) act as cell surface receptors for growth factors. Recently, the marker CD47 was found to have anti-phagocytic signals to macrophages and inhibits natural killer (NK) cells. This enabled researchers to apply CD47 as a potential target to attenuat
immune rejection

References

External links