IgGs Are Made for Walking on Bacterial and Viral Surfaces

Nat Commun. 2014 Jul 10;5:4394. doi: 10.1038/ncomms5394.

Abstract

Binding of antibodies to their cognate antigens is fundamental for adaptive immunity. Molecular engineering of antibodies for therapeutic and diagnostic purposes emerges to be one of the major technologies in combating many human diseases. Despite its importance, a detailed description of the nanomechanical process of antibody-antigen binding and dissociation on the molecular level is lacking. Here we utilize high-speed atomic force microscopy to examine the dynamics of antibody recognition and uncover a principle; antibodies do not remain stationary on surfaces of regularly spaced epitopes; they rather exhibit 'bipedal' stochastic walking. As monovalent Fab fragments do not move, steric strain is identified as the origin of short-lived bivalent binding. Walking antibodies gather in transient clusters that might serve as docking sites for the complement system and/or phagocytes. Our findings could inspire the rational design of antibodies and multivalent receptors to exploit/inhibit steric strain-induced dynamic effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Antibody Complex / chemistry
  • Antigen-Antibody Complex / immunology
  • Antigen-Antibody Complex / physiology*
  • Antigens, Bacterial / chemistry
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / physiology*
  • Antigens, Viral / chemistry
  • Antigens, Viral / immunology
  • Antigens, Viral / physiology*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / immunology
  • Bacterial Proteins / physiology
  • Capsid Proteins / chemistry
  • Capsid Proteins / immunology
  • Capsid Proteins / physiology
  • Epitopes / chemistry
  • Epitopes / immunology
  • Epitopes / physiology*
  • Humans
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / immunology
  • Immunoglobulin G / physiology*
  • Microscopy, Atomic Force
  • Protein Binding / physiology
  • Stochastic Processes

Substances

  • Antigen-Antibody Complex
  • Antigens, Bacterial
  • Antigens, Viral
  • Bacterial Proteins
  • Capsid Proteins
  • Epitopes
  • Immunoglobulin G