CD16

CD16, also known as Fc gamma receptor III (FcγRIII), is a receptor for the Fc portion of IgG antibodies. In humans there are two main isotypes: CD16a (FcγRIIIa) and CD16b (FcγRIIIb). The genes FCGR3A and FCGR3B, located on chromosome 1, encode these proteins. CD16a is a transmembrane glycoprotein expressed on natural killer (NK) cells, certain T cells, monocytes, and some dendritic cells; CD16b is a glycosylphosphatidylinositol (GPI)-anchored protein expressed mainly on neutrophils.

CD16 mediates antibody-dependent cellular cytotoxicity and immune complex handling. CD16a on NK cells binds IgG, particularly IgG1 and IgG3, and initiates cytotoxicity against antibody-coated target cells through signaling via the associated ITAM-containing FcR gamma chain. CD16b on neutrophils binds IgG immune complexes and facilitates phagocytosis, but it lacks intrinsic signaling ability and functions as an accessory receptor that modulates neutrophil responses in concert with other receptors.

Clinical relevance of CD16 includes genetic variation that influences antibody therapies. The FCGR3A V158F polymorphism alters affinity for IgG1/IgG3 and can affect responses to therapeutic monoclonal antibodies such as rituximab and cetuximab, with higher-affinity variants often associated with stronger ADCC. NK cell subsets are commonly distinguished by CD56 and CD16 expression, with CD56dim CD16+ NK cells being highly cytotoxic. Soluble CD16 can be shed from the cell surface by proteases like ADAM17 during inflammation, rising in serum under inflammatory conditions and serving as a potential research biomarker.

In laboratory settings, CD16 is used as a flow cytometry marker to identify NK cells and neutrophils and to study antibody-dependent cellular functions and immune complex biology.