Weak Fragment Crystallizable (Fc) Domain Interactions Drive the Dynamic Assembly of IgG Oligomers upon Antigen Recognition

Jürgen Strasser, Rob N. de Jong, Frank J. Beurskens, Janine Schuurman, Paul W. H. I. Parren, Peter Hinterdorfer, Johannes Preiner

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Activation of membrane receptors through clustering is a common mechanism found in various biological systems. Spatial proximity of receptors may be transduced across the membrane to initiate signaling pathways or alternatively be recognized by peripheral proteins or immune cells to trigger external effector functions. Here we show how specific immunoglobulin G (IgG) binding induces clustering of monomeric target molecules in lipid membranes through Fc-Fc interactions. We visualize and characterize the dynamic IgG oligomerization process and the molecular interactions involved using high-speed atomic force microscopy, single-molecule force spectroscopy, and quartz crystal microbalance experiments. We found that the Fc-Fc interaction strength is precisely tuned to be weak enough to prevent IgG oligomerization in solution at physiological titers, but enabling IgG oligomerization when Fabs additionally bind to their cognate surface epitopes, a mechanism that ultimately targets IgG-mediated effector functions such as classical complement activation to antigenic membranes.

Original languageEnglish
Pages (from-to)2739-2750
Number of pages12
JournalACS Nano
Volume14
Issue number3
DOIs
Publication statusPublished - 24 Mar 2020

Keywords

  • classical complement pathway
  • high-speed atomic force microscopy
  • IgG hexamers
  • IgG oligomerization
  • quartz crystal microbalance
  • receptor clustering
  • single-molecule force spectroscopy
  • Antigens/chemistry
  • Quartz Crystal Microbalance Techniques
  • Humans
  • Immunoglobulin G/immunology
  • Microscopy, Atomic Force
  • Immunoglobulin Fc Fragments/chemistry

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