Immunoglobulin G hinge region (IgG hinge) (IgG hinge)

The Immunoglobulin G (IgG) hinge region is a specialized amino acid sequence located between the CH1 and CH2 domains of the IgG heavy chain. Its primary biological function is to provide segmental flexibility, allowing the two Fab arms to move independently to bind epitopes spaced at varying distances on an antigen surface (PubMed: 25607461). Additionally, the hinge region plays a pivotal role in mediating effector functions by maintaining the proper spatial orientation required for the Fc region to interact with Fc gamma receptors (FcγRs) and the C1q component of the complement system (UniProt: P01857). In clinical medicine, this region is the specific target of the drug Imlifidase (IdeS), a cysteine protease derived from Streptococcus pyogenes that cleaves IgG at a highly conserved sequence within the hinge (PubMed: 30552146). This cleavage effectively neutralizes pathogenic IgG antibodies by separating the antigen-binding fragments from the effector Fc fragment, making it a critical target for treating highly sensitized transplant patients and certain autoimmune conditions. Furthermore, the hinge region can become an "auto-target" itself, as proteolytic cleavage can expose neoepitopes that trigger the production of anti-hinge antibodies (AHA) in chronic inflammatory diseases like rheumatoid arthritis (PubMed: 21833741).

Other names

Hinge region of IgGIgG heavy chain hingeImmunoglobulin G1 hinge regionImmunoglobulin G2 hinge regionImmunoglobulin G3 hinge regionImmunoglobulin G4 hinge region

Proteolytic cleavage of the IgG heavy chain at a specific sequence within the hinge region, resulting in the separation of the F(ab')2 and Fc fragments (PubMed: 30552146).