Cluster of differentiation

Nomenclature

The CD nomenclature was proposed and established at the 1st International Workshop and Conference on Human Leukocyte Differentiation Antigens in Paris in 1982. This system was created to classify the many monoclonal antibodies generated by different laboratories against epitopes on leukocyte surface molecules. Its use later expanded to many other cell types. A surface molecule is assigned a CD number when two specific monoclonal antibodies are shown to bind to it.

If the molecule is not well characterized or has only one monoclonal antibody, it receives the provisional indicator "w" (e.g., "CDw186"). For instance, CD2 monoclonal antibodies react with a 50-kDa transmembrane glycoprotein on T cells. Originally, the term "antigen" or "molecule" was attached to the designation (e.g., CD2 molecule), but currently "CD2" designates the molecule and "CD2 antibody" designates the antibody. Cell populations are defined using '+' or '−' to indicate expression or lack of a CD molecule; for example, a "CD34+, CD31−" cell expresses CD34 but not CD31, typically corresponding to a stem cell.

Variability in expression can be described as hi, mid, or low (or bright, mid, or dim), as seen in T cell development where cells transition from CD4mid/CD8mid double-positive to CD4hi/CD8mid.

Immunophenotyping

In immunophenotyping, the CD system identifies cells by the molecules on their surface. While a single CD marker rarely defines a cell population, combining multiple markers pinpoints very specific immune cell types. These molecules enable cell sorting through techniques like flow cytometry.

CD4 and CD8 are two common examples, typically marking helper and cytotoxic T cells, respectively, but only when paired with CD3+, since other leukocytes (like certain macrophages or dendritic cells) can also carry CD4 or CD8. HIV enters a T helper cell by binding to CD4 and a chemokine receptor. Doctors often monitor HIV progression by counting CD4 and CD8 T cells in the blood.

Physiological functions

CD molecules are not merely markers; most have important functions. CD4 and CD8 are critical in antigen recognition. Others, such as CD135, act as cell surface receptors for growth factors. CD47 provides anti-phagocytic signals to macrophages and inhibits natural killer cells, making it a potential target to attenuate immune rejection.