Immunoglobulin heavy constant gamma (IGHG)

The Human Immunoglobulin gamma (IgG) heavy chain is a central protein component of IgG antibodies, which are the primary mediators of humoral immunity in humans [1]. It consists of an N-terminal variable domain (VH) that contributes to antigen specificity and three C-terminal constant domains (CH1, CH2, and CH3) that form the Fc region responsible for interacting with immune receptors and complement proteins [2]. There are four distinct subclasses of the IgG heavy chain—IgG1, IgG2, IgG3, and IgG4—each encoded by a specific gene (IGHG1, IGHG2, IGHG3, and IGHG4) and possessing different capacities to trigger effector functions like opsonization and complement activation [3]. In therapeutic applications, the IgG heavy chain is targeted to treat severe autoimmune diseases and prevent organ transplant rejection by neutralizing pathogenic autoantibodies. For example, the drug imlifidase is a bacterial-derived enzyme that specifically cleaves the IgG heavy chain at the hinge region, effectively disarming the antibody by separating its binding site from its inflammatory signaling region [4]. Additionally, modern therapies utilize neonatal Fc receptor (FcRn) antagonists to interfere with the recycling of the IgG heavy chain, leading to a rapid reduction in circulating IgG levels and alleviating antibody-mediated pathology [5]. Citations: [1] UniProt Consortium, P01857; [2] Schroeder HW Jr, Cavacini L, J Allergy Clin Immunol (2010); [3] Vidarsson G, et al., Front Immunol (2014); [4] Jordan SC, et al., N Engl J Med (2017); [5] Ulrichts P, et al., J Clin Invest (2018).

Other names

IgG heavy chainGamma heavy chainIGHG1IGHG2IGHG3IGHG4Immunoglobulin gamma heavy chainImmunoglobulin heavy constant gamma

Direct enzymatic cleavage of the IgG hinge region by endopeptidases (e.g., imlifidase) to decouple antigen recognition from effector functions; indirect depletion via blockade of the neonatal Fc receptor (FcRn), preventing IgG recycling and promoting lysosomal degradation.