Oligomerization of Mannan-binding Lectin Dictates Binding Properties and Complement Activation.

Area of Science:

• Immunology
• Molecular Biology

Background:

• The complement system, part of innate immunity, recognizes and clears pathogens.
• The lectin pathway initiates complement activation via pattern recognition molecules (PRMs) binding to foreign surfaces.
• Mannan-binding lectin (MBL) is a key PRM, existing as various oligomers.

Purpose of the Study:

• To investigate how MBL oligomerization affects its binding to microorganisms.
• To determine the influence of MBL oligomers on interactions with MBL-associated serine proteases (MASPs) and MBL-associated proteins (MAps).
• To assess the impact of MBL oligomeric state on complement activation.

Main Methods:

• Binding assays of different MBL oligomers to Staphylococcus aureus at 37°C.
• Analysis of MBL oligomeric forms in serum complexes with MASPs and MAp44.
• Interaction studies using purified recombinant MBL (rMBL) oligomers with MASPs and MAp44.
• Complement activation assays comparing trimeric and tetrameric rMBL.

Main Results:

• Tetrameric MBL exhibited higher binding to S. aureus compared to trimeric and dimeric forms.
• Tetrameric MBL was the predominant oligomer found in serum complexes with MASPs and MAp44.
• Tetrameric rMBL showed stronger interactions with MASPs and MAp44 than trimeric rMBL.
• Trimeric rMBL was less effective than tetrameric rMBL in activating the complement system.

Conclusions:

• MBL oligomerization significantly influences its binding capabilities to microbial surfaces.
• The oligomeric state of MBL is crucial for its interaction with MASPs and MAp44.
• Tetrameric MBL demonstrates superior effector function in initiating complement activation compared to trimeric MBL.