FcR

Fc receptors (FcRs) are a family of cell-surface proteins that bind the Fc region of immunoglobulins, linking antibody recognition to effector immune functions. They are expressed on various immune and some non-immune cells and regulate processes such as phagocytosis, antibody-dependent cellular cytotoxicity (ADCC), cytokine release, and clearance of immune complexes. Fc receptors are classified by the antibody isotype they recognize, with Fc gamma receptors (FcγR) for IgG being the best studied, along with Fc alpha receptor (FcαR) for IgA and Fc epsilon receptor (FcεR) for IgE. There are also receptors that interact with IgM (FcμR) and, less commonly discussed, IgD (FcδR). In humans, FcγRs include activating receptors (such as FcγRI, FcγRIIA, FcγRIIIA) and the inhibitory FcγRIIB, which contain signaling motifs that dampen activation. FcγRIIIA and FcγRIIIB play prominent roles in ADCC, especially by natural killer cells and neutrophils. FcεRI on mast cells and basophils mediates allergic responses to IgE, while FcαRI (CD89) on myeloid cells participates in IgA-mediated responses.

Fc receptors signal through either ITAM-containing activating chains or ITIM-containing inhibitory motifs, balancing immune activation. The neonatal Fc receptor (FcRn) is a related Fc receptor that binds IgG in acidic endosomes, protecting IgG from degradation and extending half-life, and facilitating placental transfer of IgG.

Clinically, FcR interactions are central to antibody therapies; engineering Fc regions can enhance or reduce effector functions such as ADCC. Polymorphisms in FcR genes influence susceptibility to disease and responses to monoclonal antibody treatments.