Thecluster of differentiation (also known ascluster of designation orclassification determinant and often abbreviated asCD) is a protocol used for the identification and investigation ofcell surface molecules providing targets forimmunophenotyping of cells.[1] In terms of physiology, CD molecules can act in numerous ways, often acting asreceptors orligands important to the cell. Asignal cascade is usually initiated, altering the behavior of the cell (seecell signaling). Some CD proteins do not play a role in cell signaling, but have other functions, such ascell adhesion.CD for humans is numbered up to 371 (as of 21 April 2016[update]).[2][3]
TheCD nomenclature was proposed and established in the 1st International Workshop and Conference on HumanLeukocyte DifferentiationAntigens (HLDA), held inParis in 1982.[4][5] This system was intended for the classification of the manymonoclonal antibodies (mAbs) generated by different laboratories around the world againstepitopes on the surface molecules ofleukocytes (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 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").[6]
For instance,CD2 mAbs are reagents that react with a 50‐kDatransmembraneglycoprotein expressed onT 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" is generally used to designate the molecule, and "CD2antibody" is used to designate the antibody.[7]
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 astem cell, as opposed to a fully differentiatedendothelial cell. Some cell populations can also be defined ashi,mid, orlow (alternatively,bright,mid, ordim), indicating an overallvariability in CDexpression, particularly when compared to other cells being studied. A review of the development of T cells in thethymus uses this nomenclature to identify cells transitioning from CD4mid/CD8mid double-positive cells to CD4hi/CD8mid.[8]
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 | [9] |
| II | Boston | 1984 | 16-26 | [10] |
| III | Oxford | 1986 | 27-45 | [11] |
| IV | Vienna | 1989 | 46-78 | [12] |
| V | Boston | 1993 | 79-130 | [13] |
| VI | Kobe | 1996 | 131-166 | [14] |
| VII | Harrogate | 2000 | 167-247 | [15] |
| VIII | Adelaide | 2004 | 248-339 | [16] |
| IX | Barcelona | 2010 | 340-364 | [17] |
| X | Wollongong | 2014 | 365-371 |
The CD system is commonly used as cell markers inimmunophenotyping, allowing cells to be defined based on what molecules are present on their surface. These markers are often used to associate cells with certainimmune 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.[citation needed]
CD molecules are utilized incell sorting using various methods, includingflow cytometry.[citation needed]
| Type of cell | CD markers |
|---|---|
| stem cells | CD34+,CD31-,CD117 |
| allleukocyte groups | CD45+ |
| Granulocyte | CD45+,CD11b,CD15+,CD24+,CD114+, CD182+[18] |
| Monocyte | CD4, CD45+,CD14+,CD114+,CD11a, CD11b, CD91+,[18]CD16+[19] |
| T lymphocyte | CD45+,CD3+ |
| T helper cell | CD45+, CD3+,CD4+ |
| T regulatory cell | CD4,CD25,FOXP3 (a transcription factor) |
| Cytotoxic T cell | CD45+, CD3+,CD8+ |
| B lymphocyte | CD45+,CD19+,CD20+,CD24+,CD38,CD22 |
| Thrombocyte | CD45+,CD61+ |
| Natural killer cell | CD16+,CD56+, CD3-,CD31,CD30, CD38 |
Two commonly used CD molecules areCD4 andCD8, which are, in general, used as markers forhelper andcytotoxic 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 achemokine 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 ofHIV infection.[citation needed]
While CD molecules are very useful in defining leukocytes, they are not merely markers on thecell surface. Though only a fraction of known CD molecules have been thoroughly characterised, most of them have important functions. In the example of CD4 and CD8, these molecules are critical inantigen recognition. Others (e.g.,CD135) act as cell surface receptors forgrowth factors. Recently, the marker CD47 was found to have anti-phagocytic signals to macrophages and inhibitnatural killer (NK) cells. This enabled researchers to apply CD47 as a potential target to attenuateimmune rejection.[20][21]
Clarify and bring up to date earlier provisional (CDw) designations.
