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 molecule Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...

s providing targets for

immunophenotyping Immunophenotyping is a technique used to study the protein expressed by cells. This technique is commonly used in basic science research and laboratory diagnostic purpose. This can be done on tissue section (fresh or fixed tissue), cell suspensio ...

of cells. In terms of physiology, CD molecules can act in numerous ways, often acting as

receptors Receptor may refer to: *Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds ...

ligands In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's ...

important to the cell. A signal cascade is usually initiated, altering the behavior of the cell (see

cell signaling In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...

). Some CD proteins do not play a role in cell signaling, but have other functions, such as

cell adhesion Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as Cell_junction, cell junc ...

. 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 White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

Differentiation

Antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s (HLDA), held in

Paris Paris () is the Capital city, capital and List of communes in France with over 20,000 inhabitants, largest city of France. With an estimated population of 2,048,472 residents in January 2025 in an area of more than , Paris is the List of ci ...

in 1982. This system was intended for the classification of the many

monoclonal antibodies A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a Lineage (evolution), cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Mon ...

(mAbs) generated by different laboratories around the world against

epitope An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although e ...

s on the surface molecules of

leukocyte White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

s (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"). For instance, CD2 mAbs are reagents that react with a 50‐kDa

transmembrane A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently u ...

glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...

expressed on

T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...

s. 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 An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

" 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 CD34 is a transmembrane phosphoglycoprotein protein encoded by the CD34 gene in humans, mice, rats and other species. CD34 derives its name from the cluster of differentiation protocol that identifies cell surface antigens. CD34 was first desc ...

CD31 Platelet endothelial cell adhesion molecule (PECAM-1) also known as cluster of differentiation 31 (CD31) is a protein that in humans is encoded by the ''PECAM1'' gene found on chromosome 17, chromosome17q23.3. PECAM-1 plays a key role in removi ...

−" cell is one that expresses CD34 but not CD31. This CD combination typically corresponds to a

stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...

, as opposed to a fully differentiated

endothelial cell The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and th ...

. 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 The thymus (: thymuses or thymi) is a specialized primary lymphoid organ of the immune system. Within the thymus, T cells mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. The thymus ...

uses this nomenclature to identify cells transitioning from CD4^mid/CD8^mid double-positive cells to CD4^hi/CD8^mid.

Human Leukocyte Differentiation Antigen Workshops

Since 1982 there have been nine Human Leukocyte Differentiation Antigen Workshops culminating in a conference.

Immunophenotyping

The CD system is commonly used as cell markers in

, 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 function The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as cancer cells, parasitic worms, and also objects such as ...

s. 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 Cell sorting is the process through which a particular cell type is separated from others contained in a sample on the basis of its physical or biological properties, such as size, morphological parameters, viability and both extracellular and intra ...

using various methods, including

flow cytometry Flow cytometry (FC) is a technique used to detect and measure the physical and chemical characteristics of a population of cells or particles. In this process, a sample containing cells or particles is suspended in a fluid and injected into the ...

. Two commonly used CD molecules are

CD4 In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as helper T cells, monocytes, macrophages, and dendritic c ...

and

CD8 CD8 (cluster of differentiation 8) is a transmembrane protein, transmembrane glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). Along with the TCR, the CD8 co-receptor plays a role in T cell Cell signaling, signaling and aid ...

, which are, in general, used as markers for helper and

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are toxic metals, toxic chemicals, microbe neurotoxins, radiation particles and even specific neurotransmitters when the system is out of balance. Also some types of dr ...

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 A dendritic cell (DC) is an antigen-presenting cell (also known as an ''accessory cell'') of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system ...

express high levels of CD8).

Human immunodeficiency virus The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause AIDS, acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of th ...

binds CD4 and a

chemokine Chemokines (), or chemotactic cytokines, are a family of small cytokines or signaling proteins secreted by cells that induce directional movement of leukocytes, as well as other cell types, including endothelial and epithelial cells. In addit ...

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 The human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. Without treatment, it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). It is a preventable disease. It can ...

Physiological functions

While CD molecules are very useful in defining leukocytes, they are not merely markers on the

cell surface The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extra ...

. 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 in

antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

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

growth factor A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. Usually it is a secreted protein or a steroid hormone. Growth factors are important for ...

s. Recently, the marker CD47 was found to have anti-

phagocytic Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...

signals to macrophages and inhibit

natural killer Nature is an inherent character or constitution, particularly of the ecosphere or the universe as a whole. In this general sense nature refers to the laws, elements and phenomena of the physical world, including life. Although humans are par ...

(NK) cells. This enabled researchers to apply CD47 as a potential target to attenuate

immune rejection Transplant rejection occurs when Organ transplant, transplanted tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the Molecular genetics, molecular si ...

References

External links