Cluster of differentiation

The cluster of differentiation (also known as cluster of designation or classification determinantand 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 (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 signaling, but have other functions, such as cell adhesion. CD for humans is numbered up to 371
(As of April 2016).[2][3]

Contents
1 Nomenclature
2 Human Leukocyte Differentiation Antigen W
orkshops
3 Immunophenotyping
4 Physiological functions
5 See also
6 References
7 External links

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.[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").

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 .[6]

Human Leukocyte Differentiation Antigen Workshops

Since 1982 there have been nine Human Leukocyte Dif
ferentiation Antigen Workshops culminating in a conference
 Workshop City Year CDs assigned Reference

I Paris 1982 1-15 [7]

II Boston 1984 16-26 [8]

III Oxford 1986 27-45 [9]

IV Vienna 1989 46-78 [10]

V Boston 1993 79-130 [11]

VI Kobe 1996 131-166 [12]

VII Harrogate 2000 167-247 [13]

VIII Adelaide 2004 248-339 [14]

IX Barcelona 2010 340-364 [15]

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 (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.

Type of cell CD markers

stem cells CD34+, CD31-, CD117
all leukocyte
CD45+
groups

Granulocyte CD45+, CD11b, CD15+, CD24+, CD114+, CD182+[16]

Cluster of Differentiation
CD4, CD45+, CD14+, CD114+, CD11a, CD11b,
Monocyte
CD91+,[16] CD16+[17]
T lymphocyte CD45+, CD3+
T helper cell CD45+, CD3+, CD4+
T regulatory
CD4, CD25, FOXP3 (a transcription factor)
cell
Cytotoxic T
CD45+, CD3+, CD8+
cell
B lymphocyte CD45+, CD19+, CD20+, CD24+, CD38, CD22
Thrombocyte CD45+, CD61+
Natural killer
CD16+, CD56+, CD3-, CD31, CD30, CD38
cell

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 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 inantigen recognition. Others (e.g.,CD135) act as cell surface receptors for growth factors.

See also
Immune system
Immune tolerance
Antibodies
Leukocytes
List of human clusters of differentiation
Major histocompatibility complex
Signal transduction
CD13 marker for kidney disorder
CD33 marker for AML treatment

References
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(https://doi.org/1
0.1111%2Fj.1365-2559.1988.tb01967.x). PMID 3294157 (https://www.ncbi.nlm.nih.gov/pubmed/3294157).
2. "HCDM, responsible for HLDA workshop and CD molecules"(http://www.hcdm.org/MoleculeInformation/tabid/54/Def
ault.aspx). Human Cell Differentiation Molecules Council (successor to the HLDA Workshops). 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(https://doi.org/10.101
6%2Fj.jim.2006.11.001). PMID 17174972 (https://www.ncbi.nlm.nih.gov/pubmed/17174972).
4. Bernard A, Boumsell L (1984). "[Human leukocyte dif
ferentiation antigens]".Presse Med (in French). 13 (38): 2311–
6. PMID 6239187 (https://www.ncbi.nlm.nih.gov/pubmed/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 (https://www.ncbi.nlm.nih.gov/pu
bmed/6240938).
6. Ho IC, Tai TS, Pai SY (February 2009)."GATA3 and the T-cell lineage: essential functions before and after T-helper-
2-cell differentiation" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2998182). Nature Reviews Immunology. 9 (2):
125–35. doi:10.1038/nri2476 (https://doi.org/10.1038%2Fnri2476). PMC 2998182 (https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC2998182) . PMID 19151747 (https://www.ncbi.nlm.nih.gov/pubmed/19151747).
7. Bernard, AR; et al. (1984).Leucocyte Typing: Human Leucocyte Differentiation Antigens Detected by Monoclonal
antibodies. Berlin: Springer-Verlag.
8. Reinherz, EL; et al. (1985).Leukocyte Typing II. New York: Springer-Verlag.
9. McMichael, AJ; et al. (1987).Leucocyte Typing III. White Cell Differentiation Antigens. Oxford University Press.
10. Knapp, W; et al. (1989). Leucocyte Typing IV. Oxford University Press.
11. Schlossman, SF; et al. (1995).Leucocyte Typing V: White cell differentiation antigens. Oxford University Press.
12. Kishimoto, T; et al. (1997). Leucocyte Typing VI. Garland Publishing.
13. Mason, D.; et al. (2002).Leucocyte Typing VII. Oxford University Press.
14. Zola H, Swart B, Nicholson I, Aasted B, Bensussan A, Boumsell L, Buckley C, Clark G, Drbal K, Engel, Hart
P 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 dif ferentiation
molecules". Blood. 106 (9): 3123–6. doi:10.1182/blood-2005-03-1338(https://doi.org/10.1182%2Fblood-2005-03-13
38). PMID 16020511 (https://www.ncbi.nlm.nih.gov/pubmed/16020511).
15. "Proceedings of the 9th International Workshop on Human Leukocyte Differentiation Antigens. March 2010.
Barcelona, Spain". Immunol Lett. 134 (2): 103–187. 30 January 2011.
16. "CD Antigens" (http://docs.abcam.com/pdf/immunology/cdantigen_poster
.pdf) (PDF). abcam. 2009. Retrieved
2014-11-22.
17. Passlick B, Flieger D, Ziegler-Heitbrock HW (1989)."Identification and characterization of a novel monocyte
subpopulation in human peripheral blood"(http://bloodjournal.hematologylibrary.org/content/74/7/2527.long). Blood.
74 (7): 2527–2534. PMID 2478233 (https://www.ncbi.nlm.nih.gov/pubmed/2478233).

External links
Molecule search maintained by the Human Cell Differentiation Molecules Council (successor to the HLDA
Workshops)
Table of CD Antigens
CD list Protein Reviews On The Web
Yet another list of CD molecules, at PathologyOutlines.com
Wall charts of CD molecules and other cytokines, with colors, arrows from one cell to another
, from eBioscience.
Skin Research Center labHopital St Louis, Paris (France) Dir. Dr. A. Bensussan

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