Potent TRIM21 and complement-dependent intracellular antiviral immunity requires the IgG3 hinge

Area of Science:

• Immunology
• Virology
• Antibody Engineering

Background:

• Humans possess four immunoglobulin G (IgG) antibody subclasses with distinct immune functions.
• While IgG1 is prevalent in therapeutics, IgG3 shows potential for enhanced pathogen protection.

Purpose of the Study:

• To investigate the mechanisms behind IgG3's superior intracellular antiviral immunity.
• To compare the intracellular immune-mediating capacities of different IgG subclasses.

Main Methods:

• Comparative analysis of IgG subclass functions in intracellular immunity.
• Assessment of the role of the IgG hinge region in Fc receptor TRIM21 recruitment.
• Investigation of TRIM21 synergy with complement-mediated degradation pathways.

Main Results:

• IgG3 exhibits enhanced capacity for intracellular antiviral immunity compared to other IgG subclasses.
• A uniquely extended and flexible IgG3 hinge region facilitates improved TRIM21 recruitment, independent of binding affinity.
• IgG3 potentiates hinge-dependent TRIM21 synergy with complement-mediated lysosomal degradation.

Conclusions:

• IgG subclasses differentially mediate intracellular immunity.
• The IgG3 hinge region is critical for potent antiviral defense mechanisms.
• Findings can guide the selection and engineering of IgG subclasses for antiviral antibody development.