Human immunoglobulin G heavy chain hinge region (IgG hinge)

The Human immunoglobulin G (IgG) heavy chain hinge region is a specialized, flexible amino acid sequence located between the CH1 and CH2 constant domains of the IgG heavy chain [1]. Its primary biological function is to provide the Fab arms with the necessary mobility to bind bivalently to antigens at varying distances and orientations [2]. Structurally, the hinge region contains the inter-chain disulfide bridges that covalently link the two heavy chains, maintaining the overall Y-shaped architecture of the antibody [1]. In clinical medicine, this region is a critical target for Imlifidase (IdeS), a cysteine protease that specifically cleaves the IgG hinge to separate the Fab fragments from the Fc region [3]. This cleavage effectively abolishes the antibody's ability to trigger complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) [4]. Consequently, the IgG hinge region is a focal point for therapeutic intervention in antibody-mediated rejection during organ transplantation and in severe autoimmune diseases [3, 5]. Citations: [1] UniProt Consortium, P01857; [2] Roux, K. H., et al. (1997) J Immunol; [3] Jordan, S. C., et al. (2017) N Engl J Med; [4] Hansson, S., et al. (2020) Curr Opin Organ Transplant; [5] Lonze, B. E., et al. (2018) Am J Transplant.

Other names

IgG hinge regionImmunoglobulin G hingeHinge domain of IgGIgG heavy chain hinge

Proteolytic cleavage of the hinge region at a specific amino acid sequence (e.g., Gly-Pro-Ser-Val-Phe-Leu-Phe) to separate the antigen-binding Fab fragments from the effector-mediating Fc fragment, thereby neutralizing antibody effector functions [3, 4].