Crystallization of a complex between the Fab fragment of a human immunoglobulin M (IgM) rheumatoid factor (RF-AN) and the Fc fragment of human IgG4

Immunology. 1996 Aug;88(4):636-41. doi: 10.1046/j.1365-2567.1996.d01-692.x.

Abstract

Rheumatoid factors (RF) are the characteristic autoantibodies found in patients with rheumatoid arthritis. They recognize epitopes in the Fc region of immunoglobulin G (IgG) and are often of the IgM isotype. In order to analyse the nature of RF-Fc interactions, we have crystallized a complex between the Fab fragment of a human monoclonal IgM rheumatoid factor (RF-AN) and the Fc fragment of human IgG4. The stoichiometry of the complex within the crystals was found to be 2:1 Fab:Fc. The crystals diffracted X-rays to 0.3 nm resolution, and the space group was C2, with cell dimensions a = 16.03 nm, b = 8.19 nm, c = 6.42 nm, beta = 98.3 degrees. We have also determined the sequence of the variable region of the RF-AN light chain, not hitherto reported. This belongs to the V lambda III-a subgroup and is closely related to the germline gene Humlv318, from which it differs in three amino acid residues. This is the first reported crystallized complex between a human autoantibody and its autoantigen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigen-Antibody Complex / chemistry*
  • Antigen-Antibody Complex / genetics
  • Base Sequence
  • Crystallization
  • Humans
  • Immunoglobulin Fab Fragments / immunology*
  • Immunoglobulin Fc Fragments / immunology*
  • Immunoglobulin G / immunology*
  • Immunoglobulin M / immunology
  • Immunoglobulin Variable Region / genetics
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Rheumatoid Factor / immunology*

Substances

  • Antigen-Antibody Complex
  • Immunoglobulin Fab Fragments
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunoglobulin Variable Region
  • Rheumatoid Factor