Fc domain of Immunoglobulin G (IgG Fc)

The Fc (fragment crystallizable) domain of Immunoglobulin G (IgG) is the tail region of the antibody molecule, consisting of the CH2 and CH3 constant domains (UniProt P01857). It mediates critical immune effector functions by binding to Fc gamma receptors (FcγRs) on immune cells and the C1q component of the complement system (Janeway's Immunobiology). Furthermore, the Fc domain interacts with the neonatal Fc receptor (FcRn), which regulates IgG homeostasis and extends its serum half-life (Roopenian & Akilesh, 2007). In autoimmune diseases and transplantation, the Fc domain of pathogenic IgGs drives inflammation and tissue destruction (PMID: 28767351). Therapeutic agents like Imlifidase (IdeS) target this domain by cleaving the IgG hinge region, thereby neutralizing its effector capabilities (Hansa Biopharma). This approach is particularly vital for treating acute antibody-mediated rejection and severe autoimmune conditions where rapid IgG clearance is required. Additionally, the Fc domain of therapeutic antibodies is often engineered to enhance or reduce these effector functions depending on the desired clinical outcome (PMID: 17703228). Understanding the structural and functional nuances of the Fc domain is essential for the development of both IgG-based therapeutics and agents designed to modulate endogenous antibody activity.

Other names

Fragment crystallizable region of IgGIgG Fc regionCH2-CH3 domainImmunoglobulin G Fc fragment

Proteolytic cleavage of the IgG hinge region to separate the Fc domain from the antigen-binding (Fab) fragments, thereby abolishing Fc-mediated effector functions and complement activation (PMID: 28767351).