Revised porcine IgG subclass classification based on innate immune cell activation

Area of Science:

• Immunology
• Molecular Biology
• Structural Biology

Background:

• Current porcine immunoglobulin G (IgG) subclass classification lacks functional predictive power.
• Phylogenetic analysis of gene sequences results in an inadequate nomenclature for understanding biological roles.

Purpose of the Study:

• To propose a revised, functionality-based nomenclature for porcine IgG subclasses.
• To re-analyze Fc domain interaction motifs and in vitro effector functions for a predictive framework.

Main Methods:

• Production of twelve recombinant porcine IgG subclasses.
• Evaluation of reactive oxygen species (ROS) production in monocytes and neutrophils.
• In silico analysis of Fc domain interaction motifs and complement activation determinants.

Main Results:

• Porcine IgG4 family subclasses (IgG4a-d) uniquely induced significant respiratory burst via a Glycine-Proline (GP) motif.
• Complement activation is influenced by a "PAP" motif and Lysine-320 (K320), with mutations affecting activity.
• The ancestral pIgG3 Fc domain is functionally inert due to a P329L mutation disrupting Fcγ receptor binding.

Conclusions:

• A functional dichotomy exists among porcine IgG subclasses, challenging previous assumptions about pIgG1.
• Specific amino acid motifs (GP, PAP, K320) are critical for IgG effector functions like ROS production and complement activation.
• The proposed functional nomenclature offers a predictive framework for porcine immunology and IgG subclass diversification.