Human immunoglobulin G Fc CH2 domain (CH2) (CH2)

The Human Immunoglobulin G (IgG) Fc CH2 domain is a critical structural and functional component of the IgG antibody's constant region (Vidarsson et al., 2014, Frontiers in Immunology). Located between the hinge region and the CH3 domain, it serves as the primary binding site for C1q to initiate the classical complement pathway and for various Fc gamma receptors (FcγRs) that mediate effector functions like antibody-dependent cellular cytotoxicity (ADCC) (Sondermann et al., 2000, Nature). A defining feature of the CH2 domain is the conserved N-linked glycosylation site at Asparagine 297; the specific carbohydrate structures attached here are essential for maintaining the domain's stability and its affinity for Fc receptors (Houde et al., 2010, Molecular & Cellular Proteomics). In therapeutic development, the CH2 domain is frequently engineered to either enhance or silence these effector functions, or to improve the pharmacokinetic profile of monoclonal antibodies and Fc-fusion proteins (Strohl, 2009, Current Opinion in Biotechnology). Furthermore, the interface between the CH2 and CH3 domains is the binding site for the neonatal Fc receptor (FcRn), which protects IgG from degradation and extends its serum half-life (Kuo et al., 2010, Journal of Biological Chemistry). This makes the domain a focal point for drugs like efgartigimod, designed to treat autoimmune conditions by accelerating the clearance of pathogenic IgG (Ulrichts et al., 2018, Journal of Clinical Investigation). Understanding the structural dynamics of the CH2 domain is vital for the design of next-generation biologics with optimized safety and efficacy profiles.

Other names

Cgamma2 domainSecond constant domain of the IgG heavy chainIgG CH2 domain

Competitive inhibition of neonatal Fc receptor (FcRn) binding to the IgG Fc region to accelerate pathogenic IgG clearance, and modulation of Fcγ receptor and C1q binding to regulate immune effector functions.