Cluster of differentiation

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.[1] 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).[2][3]


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.[4][5] 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 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" is generally used to designate the molecule, and "CD2 antibody" is used to designate the antibody.[6]

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(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 uses this nomenclature to identify cells transitioning from CD4mid/CD8mid double positive cells to CD4hi/CD8mid.[7]

Human Leukocyte Differentiation Antigen WorkshopsEdit

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 [8]
II Boston 1984 16-26 [9]
III Oxford 1986 27-45 [10]
IV Vienna 1989 46-78 [11]
V Boston 1993 79-130 [12]
VI Kobe 1996 131-166 [13]
VII Harrogate 2000 167-247 [14]
VIII Adelaide 2004 248-339 [15]
IX Barcelona 2010 340-364 [16]
X Wollongong 2014 365-371


Cluster of Differentiation

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.[citation needed]

CD molecules are utilized in cell sorting using various methods, including flow cytometry.

Type of cell CD markers
stem cells CD34+, CD31-, CD117
all leukocyte groups CD45+
Granulocyte CD45+, CD11b, CD15+, CD24+, CD114+, CD182+[17]
Monocyte CD4, CD45+, CD14+, CD114+, CD11a, CD11b, CD91+,[17] CD16+[18]
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 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 (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 functionsEdit

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 (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 inhibits natural killer (NK) cells. This enabled researchers to apply CD47 as a potential target to attenuate immune rejection.[19]

See alsoEdit


  1. ^ CHAN, J. K. C.; NG, C. S.; HUI, P. K. (1988). "A simple guide to the terminology and application of leucocyte monoclonal antibodies". Histopathology. 12 (5): 461–480. doi:10.1111/j.1365-2559.1988.tb01967.x. PMID 3294157. S2CID 6823812.
  2. ^ "HCDM, responsible for HLDA workshop and CD molecules". Human Cell Differentiation Molecules Council (successor to the HLDA Workshops). Archived from the original on 2016-04-20. Retrieved 2016-04-21.
  3. ^ Zola H, Swart B, Banham A, Barry S, Beare A, Bensussan A, Boumsell L, D Buckley C, Bühring HJ, Clark G, Engel P, Fox D, Jin BQ, Macardle PJ, Malavasi F, Mason D, Stockinger H, Yang X (2007). "CD molecules 2006--human cell differentiation molecules". J Immunol Methods. 319 (1–2): 1–5. doi:10.1016/j.jim.2006.11.001. PMID 17174972.
  4. ^ Bernard A, Boumsell L (1984). "[Human leukocyte differentiation antigens]". Presse Med (in French). 13 (38): 2311–6. PMID 6239187.
  5. ^ Fiebig H, Behn I, Gruhn R, Typlt H, Kupper H, Ambrosius H (1984). "Charakterisierung einer Serie von monoklonalen Antikörpern gegen humane T-Zellen" [Characterization of a series of monoclonal antibodies against human T cells]. Allerg Immunol (Leipz) (in German). 30 (4): 242–50. PMID 6240938.
  6. ^ Beare, Alice; Stockinger, Hannes; Zola, Heddy; Nicholson, Ian (2008). "Monoclonal Antibodies to Human Cell Surface Antigens". Current Protocols in Immunology. 80: 4A. doi:10.1002/0471142735.ima04as80. PMC 7162157. PMID 18432634.
  7. ^ Ho IC, Tai TS, Pai SY (February 2009). "GATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation". Nature Reviews Immunology. 9 (2): 125–35. doi:10.1038/nri2476. PMC 2998182. PMID 19151747.
  8. ^ Bernard, AR; et al. (1984). Leucocyte Typing: Human Leucocyte Differentiation Antigens Detected by Monoclonal antibodies. Berlin: Springer-Verlag.
  9. ^ Reinherz, EL; et al. (1985). Leukocyte Typing II. New York: Springer-Verlag.
  10. ^ McMichael, AJ; et al. (1987). Leucocyte Typing III. White Cell Differentiation Antigens. Oxford University Press.
  11. ^ Knapp, W; et al. (1989). Leucocyte Typing IV. Oxford University Press.
  12. ^ Schlossman, SF; et al. (1995). Leucocyte Typing V: White cell differentiation antigens. Oxford University Press.
  13. ^ Kishimoto, T; et al. (1997). Leucocyte Typing VI. Garland Publishing.
  14. ^ Mason, D.; et al. (2002). Leucocyte Typing VII. Oxford University Press.
  15. ^ Zola H, Swart B, Nicholson I, Aasted B, Bensussan A, Boumsell L, Buckley C, Clark G, Drbal K, Engel P, Hart D, Horejsí V, Isacke C, Macardle P, Malavasi F, Mason D, Olive D, Saalmueller A, Schlossman SF, Schwartz-Albiez R, Simmons P, Tedder TF, Uguccioni M, Warren H (November 1, 2005). "CD molecules 2005: human cell differentiation molecules". Blood. 106 (9): 3123–6. doi:10.1182/blood-2005-03-1338. PMID 16020511.
  16. ^ "Proceedings of the 9th International Workshop on Human Leukocyte Differentiation Antigens. March 2010. Barcelona, Spain". Immunol. Lett. 134 (2): 103–187. 30 January 2011.
  17. ^ a b "CD Antigens" (PDF). abcam. 2009. Retrieved 2014-11-22.
  18. ^ Passlick B, Flieger D, Ziegler-Heitbrock HW (1989). "Identification and characterization of a novel monocyte subpopulation in human peripheral blood". Blood. 74 (7): 2527–2534. doi:10.1182/blood.V74.7.2527.2527. PMID 2478233.
  19. ^ Deuse, T; Hu, X (2019). "Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients". Nature Biotechnology. 37 (3): 252–258. doi:10.1038/s41587-019-0016-3. PMC 6419516. PMID 30778232.

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