Human IgG2 is one of the four subclasses of immunoglobulin G (IgG) in humans, alongside IgG1. IgG3. and IgG4. It constitutes approximately 20-30% of total serum IgG and plays a distinct role in adaptive immunity. Structurally, IgG2 features a unique hinge region with shorter flexibility compared to IgG1 and IgG3. along with specific disulfide bond patterns that influence its antigen-binding fragment (Fab) flexibility and Fc-mediated effector functions. These structural characteristics contribute to its restricted ability to engage Fc gamma receptors (FcγRs) and activate complement pathways, making IgG2 less potent in triggering antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) compared to IgG1.
Biologically, IgG2 antibodies are often associated with responses to polysaccharide antigens, such as those found in bacterial capsules, and are predominant in immunity against encapsulated pathogens. Their limited effector functions may reduce inflammatory side effects, making IgG2 a preferred scaffold for therapeutic antibodies where minimal immune activation is desirable. For example, certain monoclonal antibody drugs targeting chronic inflammatory conditions or tumors leverage IgG2's properties to balance efficacy and tolerability.
However, IgG2's stability and long serum half-life (～21 days) align with other IgG subclasses, supporting its therapeutic utility. Recent studies also highlight IgG2's potential in bispecific antibody engineering due to its structural adaptability. Despite its lower effector activity, IgG2 remains a critical component in both natural immune defense and biopharmaceutical applications.