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

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 crystalliz ed a complex between the Fab fragment of a human monoclonal IgM rheuma toid factor (RF-AN) and the Fc fragment of human IgG4. The stoichiomet ry 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 w as C2, with cell dimensions a = 16.03 nm, b = 8.19 nm, c = 6.42 nm, be ta = 98.3 degrees. We have also determined the sequence of the variabl e region of the RF-AN light chain, not hitherto reported. This belongs to the VlambdaIII-a subgroup and is closely related to the germline g ene Humlv318, from which it differs in three amino acid residues. This is the first reported crystallized complex between a human autoantibo dy and its autoantigen.