The cluster of differentiation 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. 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, which was held in Paris in 1982. This system was intended for the classification of the many monoclonal antibodies generated by different laboratories around the world against epitopes on the surface molecules of leukocytes. 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 the molecule. If the molecule has not been well characterized, or has only one mAb, it is usually given the provisional indicator "w". For instance, CD2 mAbs are reagents that react with a 50‐kDa transmembrane glycoprotein expressed on T cells. Later, 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. 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 a stem cell, as opposed to a fully differentiated endothelial cell. Some cell populations can also be defined as hi, mid or low, 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 CD4mid/CD8mid double positive cells to CD4hi/CD8mid.
Since 1982 there have been nine Human Leukocyte Differentiation Antigen Workshops culminating in a conference.
Workshop
City
Year
CDs assigned
Reference
I
Paris
1982
1-15
II
Boston
1984
16-26
III
Oxford
1986
27-45
IV
Vienna
1989
46-78
V
Boston
1993
79-130
VI
Kobe
1996
131-166
VII
Harrogate
2000
167-247
VIII
Adelaide
2004
248-339
IX
Barcelona
2010
340-364
X
Wollongong
2014
365-371
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, 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, 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. Human immunodeficiency virus 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 recognition. Others 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 cells. This enabled researchers to apply CD47 as a potential target to attenuate .
