Immunoglobulin G Fc domain (IgG Fc)

The Immunoglobulin G (IgG) Fc domain is the C-terminal region of the IgG antibody, composed of two identical protein fragments derived from the second and third constant domains of the antibody's heavy chains (StatPearls). It serves as the critical link between the adaptive immune system's specificity and the innate immune system's effector functions by binding to Fc gamma receptors (FcγRs) and the C1q component of the complement system (Janeway's Immunobiology). This interaction triggers processes such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Furthermore, the Fc domain binds to the neonatal Fc receptor (FcRn) in a pH-dependent manner, which protects IgG from lysosomal degradation and extends its circulating half-life to approximately 21 days (Nature Reviews Drug Discovery). In therapeutic applications, the Fc domain is frequently fused to other proteins to create Fc-fusion drugs, significantly improving their pharmacokinetic profiles. Conversely, in autoimmune diseases, the Fc-FcRn interaction is targeted by novel inhibitors like efgartigimod to accelerate the clearance of harmful autoantibodies (NEJM).

Other names

Fc regionFragment crystallizable regionIgG Fc fragmentC-terminal region of IgG heavy chain

The IgG Fc domain functions by binding to Fc gamma receptors (FcγRs) to initiate immune effector responses and to the neonatal Fc receptor (FcRn) to maintain IgG homeostasis (Nature Reviews Immunology). Therapeutic strategies targeting this domain include the use of FcRn antagonists, which competitively bind to the Fc-binding site on FcRn, thereby preventing the recycling of endogenous IgG and promoting the degradation of pathogenic autoantibodies (Lancet Neurology). Additionally, the Fc domain is utilized in Fc-fusion proteins to leverage the FcRn-mediated recycling pathway, extending the therapeutic window of the fused protein (Journal of Controlled Release).