Low affinity immunoglobulin gamma Fc receptor III-A (FCGR3A)

Low affinity immunoglobulin gamma Fc receptor III-A (FCGR3A), commonly known as CD16a, is a cluster of differentiation molecule found on the surface of natural killer (NK) cells, monocytes, and macrophages (UniProt: P08637). It serves as a critical link between the humoral and cellular immune responses by binding the Fc portion of IgG1 and IgG3 antibodies (NCBI Gene: 2214). Upon binding to antibody-coated target cells, such as tumor cells, FcγRIIIa triggers Antibody-Dependent Cellular Cytotoxicity (ADCC), a process involving the release of cytotoxic granules like perforin and granzymes (StatPearls: Antibody-Dependent Cell-Mediated Cytotoxicity). This receptor is a primary mediator of the clinical efficacy of many therapeutic monoclonal antibodies, including rituximab and trastuzumab (Wang et al., 2015, 'The role of FcγRIIIa in the mechanism of action of therapeutic antibodies'). Genetic variations in the FCGR3A gene, specifically the V158F polymorphism, affect the receptor's affinity for IgG and have been shown to correlate with patient response to antibody therapies in various cancers (PubMed: 12444030). Modern drug development often involves Fc-engineering to enhance the binding affinity of antibodies to FcγRIIIa to boost ADCC-mediated tumor clearance, as seen with the approval of margetuximab (FDA: Margenza Prescribing Information).

Other names

CD16aFc-gamma RIIIaFcRIIIaCD16A antigenFCG3FCGR3IGFR3

Binding of the Fc region of IgG antibodies to FcγRIIIa on effector cells (NK cells, macrophages) triggers Antibody-Dependent Cellular Cytotoxicity (ADCC) and phagocytosis of antibody-coated target cells.