Neonatal Fc receptor and Fc-gamma receptors (FcRn and FcγR)

The Neonatal Fc receptor (FcRn) and Fc-gamma receptors (FcγRs) are distinct but functionally related proteins that mediate the transport, homeostasis, and effector functions of Immunoglobulin G (IgG). FcRn, a heterodimer of the FCGRT and B2M gene products, is responsible for the long half-life of IgG by salvaging it from lysosomal degradation within endothelial and epithelial cells (Roopenian & Akilesh, 2007, Nature Reviews Immunology). FcγRs, including the activating receptors FcγRI (CD64), FcγRIIA (CD32a), and FcγRIIIA (CD16a), as well as the inhibitory FcγRIIB (CD32b), are expressed on leukocytes and trigger cellular responses like phagocytosis and antibody-dependent cellular cytotoxicity (ADCC) (Nimmerjahn & Ravetch, 2008, Nature Reviews Immunology). In therapeutic contexts, FcRn is targeted by FcRn antagonists such as efgartigimod to treat autoimmune conditions like myasthenia gravis by lowering pathogenic IgG levels (Gable et al., 2021, Drugs). Conversely, the Fc regions of therapeutic monoclonal antibodies are often engineered to enhance their affinity for FcγRs to improve anti-tumor efficacy in oncology (Wang et al., 2018, Frontiers in Immunology).

Other names

IgG Fc receptorsFc-gamma receptor familyNeonatal Fc receptor for IgGFCGRFCGRT

FcRn antagonists bind to the IgG-binding site of FcRn, preventing the recycling of endogenous IgG and leading to its rapid lysosomal degradation, thereby reducing the concentration of circulating pathogenic autoantibodies (Gable et al., 2021, Drugs). Therapeutic antibodies targeting FcγRs typically utilize their Fc domain to cross-link these receptors on effector cells, inducing ADCC or ADCP against target cells, or are engineered to selectively bind inhibitory FcγRIIB to suppress inflammatory responses (Nimmerjahn & Ravetch, 2008, Nature Reviews Immunology).