Cluster of differentiation

Overview
The cluster of differentiation (CD) is a protocol used for the identification and investigation of cell surface molecules present on leukocytes. CD molecules can act in numerous ways, often acting as receptors or ligands (the molecule that activates a receptor) 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 signalling, but have other functions, such as cell adhesion.

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 surface molecules of leukocytes (white blood cells). Since then, its use has expanded to many other cell types, and more than 320 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").

Uses as cell markers
The CD system is commonly used as cell markers; this allows 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 or properties. 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. 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 a stem cell, opposed to a fully differentiated endothelial cell.

Two commonly used CD molecules are CD4 and CD8, which are generally used as markers for helper and cytotoxic T cells, respectively. When defining T cells, 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). CD4 is also an essential receptor during HIV infection, allowing the HIV to bind to the helper T cell and destruction of CD4+ T cells. The relative abundance of CD4+ and CD8+ T cells is often used to monitor the progression of an HIV infection.

Other uses
It is important to note that 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 recognition.