Human immunoglobulin G3 (IgG3) is one of the four subclasses of IgG antibodies, playing a distinct role in adaptive immunity. It constitutes approximately 5-8% of total serum IgG and is characterized by a uniquely long hinge region, contributing to its structural flexibility and functional diversity. This extended hinge enhances antigen-binding avidity and facilitates interactions with immune cells, though it also makes IgG3 more susceptible to proteolytic cleavage compared to other IgG subclasses.
IgG3 exhibits strong effector functions, including high affinity for activating Fcγ receptors (FcγRI, FcγRIIa, FcγRIIIa) and potent complement activation via the classical pathway. These properties make it particularly effective in neutralizing pathogens, opsonizing targets for phagocytosis, and triggering inflammatory responses. However, its short serum half-life (~7–8 days vs. ~21 days for IgG1) limits its persistence in circulation.
Genetically, IgG3 is encoded by the IGHG3 gene on chromosome 14q32. Polymorphisms in its heavy chain constant region contribute to interindividual variability in immune responses. Clinically, IgG3 is associated with protection against encapsulated bacteria, viruses (e.g., HIV, influenza), and parasites. Conversely, it has been implicated in autoimmune disorders (e.g., lupus) and alloimmune reactions due to its proinflammatory potential.
Recent research explores engineering IgG3-based therapeutics to leverage its potent effector mechanisms while addressing stability challenges, highlighting its untapped potential in immunotherapy.