Immunoglobulin G2 (IgG2)

Immunoglobulin G2 (IgG2) is one of the four subclasses of human Immunoglobulin G, representing approximately 20-25% of the total IgG in adult serum. It is structurally distinguished by a relatively short hinge region containing four interchain disulfide bonds, which imparts a more rigid conformation compared to other IgG subclasses and limits its flexibility. Biologically, IgG2 plays a critical role in the humoral immune response against T-cell independent antigens, particularly the capsular polysaccharides of encapsulated bacteria such as Streptococcus pneumoniae and Haemophilus influenzae. Unlike IgG1 and IgG3, IgG2 has a low affinity for most Fc gamma receptors (with the notable exception of the H131 variant of FcγRIIa) and shows minimal ability to activate the classical complement pathway. In the pharmaceutical industry, the IgG2 constant region is frequently utilized as a scaffold for therapeutic monoclonal antibodies (e.g., Panitumumab, Denosumab) when reduced effector functions like antibody-dependent cellular cytotoxicity (ADCC) are desired to improve safety. While not a primary therapeutic target for inhibition, IgG2 levels are clinically significant in the diagnosis of selective immunodeficiencies, and its systemic levels can be modulated by FcRn-targeting therapies.

Other names

IgG2 subclassGamma-2 globulinHuman IgG2IGHG2

Inhibition of FcRn-mediated recycling of IgG subclasses, leading to increased degradation and reduction of serum IgG2 levels; or passive replacement therapy in deficiency states.