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

T. R. Kjaer, L. Jensen, A. Hansen, R. Dani, J. C. Jensenius, J. Dobó, P. Gál, S. Thiel

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The complement system is a part of the innate immune system and is involved in recognition and clearance of pathogens and altered-self structures. The lectin pathway of the complement system is initiated when soluble pattern recognition molecules (PRMs) with collagen-like regions bind to foreign or altered self-surfaces. Associated with the collagen-like stems of these PRMs are three mannan-binding lectin (MBL)-associated serine proteases (MASPs) and two MBL-associated proteins (MAps). The most studied of the PRMs, MBL, is present in serum mainly as trimeric and tetrameric oligomers of the structural subunit. We hypothesized that oligomerization of MBL may influence both the potential to bind to micro organisms and the interaction with the MASPs and MAps, thus influencing the ability to initiate complement activation. When testing binding at 37 °C, we found higher binding of tetrameric MBL to Staphylococcus aureus (S. aureus) than trimeric and dimeric MBL. In serum, we found that tetrameric MBL was the main oligomeric form present in complexes with the MASPs and MAp44. Such preference was confirmed using purified forms of recombinant MBL (rMBL) oligomers, where tetrameric rMBL interacted stronger with all of the MASPs and MAp44, compared to trimeric MBL. As a direct consequence of the weaker interaction with the MASPs, we found that trimeric rMBL was inferior to tetrameric rMBL in activating the complement system. Our data suggest that the oligomeric state of MBL is crucial both for the binding properties and the effector function of MBL.

Original languageEnglish
Pages (from-to)12-19
Number of pages8
JournalScandinavian Journal of Immunology
Volume84
Issue number1
DOIs
Publication statusPublished - Jul 1 2016

ASJC Scopus subject areas

  • Immunology

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