IgG1IgG3

IgG1 and IgG3 are two of the four human immunoglobulin G (IgG) subclasses. They are the most functionally active in terms of Fc-mediated effector functions and are predominant in responses to protein antigens. Like all IgG molecules, they consist of two identical heavy chains (gamma chains) and two light chains. IgG3 is distinguished by a relatively long hinge region, which confers greater flexibility but makes it more susceptible to proteolysis and gives it a shorter serum half-life than IgG1, which has a shorter hinge and a longer half-life of about 21 days. In human serum, IgG1 accounts for roughly 60–70% of IgG, while IgG3 comprises about 5–8%.

IgG1 and IgG3 are adept at engaging Fc gamma receptors (FcγRs) and activating the classical complement pathway via C1q. IgG3, in particular, binds FcγRs with higher affinity and is a potent activator of complement, contributing to strong effector functions. Consequently, these subclasses commonly mediate antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC) more effectively than IgG2 or IgG4.

Their clinical and functional relevance is broad. In infections and vaccination, IgG1 and IgG3 responses often correlate with protection, though the relative contributions vary by antigen. They cross the placenta to provide fetal protection, with IgG1 transferring efficiently and IgG3 transfer being somewhat less robust due to its shorter half-life. In autoimmune diseases, IgG1 and IgG3 autoantibodies can drive tissue injury through complement activation and Fc receptor–mediated pathways.

Therapeutically, many monoclonal antibodies use an IgG1 backbone to maximize effector functions, while engineering can tune Fc receptor binding and half-life. IgG3-based therapeutics have been explored but face challenges related to stability and pharmacokinetics.