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

M. K. Sohi, A. L. Corper, T. Wan, M. Steinitz, R. Jefferis, D. Beale, M. He, A. Feinstein, B. J. Sutton*, M. J. Taussig

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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, β = 98.3°. We have also determined the sequence of the variable region of the RF-AN light chain, not hitherto reported. This belongs to the V(λ)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.

Original languageEnglish
Pages (from-to)636-641
Number of pages6
JournalImmunology
Volume88
Issue number4
DOIs
StatePublished - 1996

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