The binding of human complement component C4 to antibody-antigen aggregates.

Area of Science:

• Immunology
• Biochemistry
• Molecular Biology

Background:

• The complement system is a critical part of innate immunity.
• Antibody-antigen complexes initiate complement activation.
• Understanding the molecular interactions in complement is vital for immunology.

Purpose of the Study:

• To investigate the binding of human complement component C4 to antibody-antigen aggregates.
• To elucidate the nature of the interaction between C4b and immunoglobulin G (IgG).
• To determine the functional consequences of C4 binding on complement activity.

Main Methods:

• Incubation of antibody-antigen aggregates with complement component C4.
• Analysis of C4 cleavage products (C4b) and their binding to aggregates.
• Biochemical characterization of C4b-IgG complexes using reduction and radioactive labeling.
• Assay of C3 convertase activity.

Main Results:

• C4 rapidly cleaves to C4b upon binding to C1-activated aggregates, with most C4b remaining in fluid phase.
• A stable, likely covalent, complex forms between C4b and IgG.
• Reduction of the C4b-IgG complex reveals specific chain interactions.
• C4b-IgG complexes exhibit maximal C3 convertase activity under specific conditions.
• C4b can also form dimers with itself, suggesting self-interaction.

Conclusions:

• A reactive group generated during C4 activation by C1 mediates covalent binding to IgG and other C4b molecules.
• This interaction is independent of transglutaminase (factor XIII) but sensitive to polyamines.
• The findings provide insight into the molecular mechanisms of complement activation and immune complex clearance.