Structure of human IgM rheumatoid factor Fab bound to its autoantigen IgG Fc reveals a novel topology of antibody-antigen interaction

Nat Struct Biol. 1997 May;4(5):374-81. doi: 10.1038/nsb0597-374.


Rheumatoid factors are the characteristic autoantibodies of rheumatoid arthritis, which bind to the Fc regions of IgG molecules. Here we report the crystal structure of the Fab fragment of a patient-derived IgM rheumatoid factor (RF-AN) complexed with human IgG4 Fc, at 3.2 A resolution. This is the first structure of an autoantibody-autoantigen complex. The epitope recognised in IgG Fc includes the C gamma 2/C gamma 3 cleft region, and overlaps the binding sites of bacterial Fc-binding proteins. The antibody residues involved in autorecognition are all located at the edge of the conventional combining site surface, leaving much of the latter available, potentially, for recognition of a different antigen. Since an important contact residue is somatic mutation, the structure implicates antigen-driven selection, following somatic mutation of germline genes, in the production of pathogenic rheumatoid factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Antibody Reactions*
  • Autoantigens / chemistry*
  • Bacterial Proteins / chemistry
  • Crystallography, X-Ray
  • Epitopes / chemistry
  • Humans
  • Immunoglobulin Fab Fragments / chemistry*
  • Immunoglobulin Fc Fragments / chemistry
  • Immunoglobulin G / chemistry
  • Immunoglobulin M / chemistry*
  • Models, Molecular
  • Oligosaccharides / chemistry
  • Rheumatoid Factor / chemistry*
  • Staphylococcal Protein A / chemistry


  • Autoantigens
  • Bacterial Proteins
  • Epitopes
  • IgG Fc-binding protein, Streptococcus
  • Immunoglobulin Fab Fragments
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Immunoglobulin M
  • Oligosaccharides
  • Staphylococcal Protein A
  • Rheumatoid Factor

Associated data

  • PDB/1ADQ