Immunoglobulin gamma 1 Fc region (IgG1 Fc)

The Human IgG1 Fc region is the C-terminal portion of the immunoglobulin G1 heavy chain, composed of the CH2 and CH3 constant domains. It serves as the critical link between the adaptive immune system's specificity and innate effector mechanisms by binding to Fc gamma receptors (FcγRs) on immune cells and the C1q component of the complement system [Vidarsson et al., 2014]. A primary physiological function of this region is its pH-dependent interaction with the neonatal Fc receptor (FcRn), which rescues IgG from lysosomal degradation in endothelial and myeloid cells, thereby maintaining its long circulatory half-life of approximately 21 days [Roopenian & Akilesh, 2007]. In therapeutic contexts, the IgG1 Fc region is targeted by enzymes like imlifidase, which cleaves the region to rapidly eliminate pathogenic IgG in sensitized transplant patients or autoimmune crises [Lonze et al., 2018]. Additionally, it is the functional target of a new class of FcRn antagonists designed to lower systemic IgG levels by blocking the recycling pathway, providing a targeted approach for treating autoantibody-mediated diseases such as myasthenia gravis [Ulrichts et al., 2018]. The region is also extensively used in biotechnology as a scaffold for Fc-fusion proteins to enhance the stability and pharmacokinetics of therapeutic peptides and cytokines.

Other names

Fragment crystallizable region of IgG1Fc gamma 1 regionIgG1 Fc fragmentIGHG1 Fc

Direct proteolytic cleavage of the hinge region to disable effector functions (e.g., imlifidase) or competitive inhibition of the neonatal Fc receptor (FcRn) to prevent IgG recycling and promote lysosomal degradation (e.g., FcRn blockers).