ArticleJournal of molecular biology2007
Crystal structure of a human autoimmune complex between IgM rheumatoid factor RF61 and IgG1 Fc reveals a novel epitope and evidence for affinity maturation.
Article in Journal of molecular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 85 citations in OpenAlex.
- i-shaped antibody engineering enables conformational tuning of biotherapeutic receptor agonists.Nature communications · 2024Article
- Characterization of Peptide Antibodies by Epitope Mapping Using Resin-Bound and Soluble Peptides.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Production of Antibodies to Peptide Targets Using Hybridoma Technology.Methods in molecular biology (Clifton, N.J.) · 2024Article
- False-positive colloidal gold-based immunochromatographic strip assay reactions for antibodies to SARS-CoV-2 in patients with autoimmune diseases.Annals of translational medicine · 2021Article
- Structural Basis of a Conventional Recognition Mode of IGHV1-69 Rheumatoid Factors.Advances in experimental medicine and biology · 2021Review
- Loop Grafting between Similar Local Environments for Fc-Silent Antibodies.Journal of chemical information and modeling · 2020Article
- Age-associated changes in the circulating human antibody repertoire are upregulated in autoimmunity.Immunity & ageing : I & A · 2020Article
- Fine Mapping of Glutamate Decarboxylase 65 Epitopes Reveals Dependency on Hydrophobic Amino Acids for Specific Interactions.International journal of molecular sciences · 2019Article
- CmAbs · 2019Article
- Two subgroups in systemic lupus erythematosus with features of antiphospholipid or Sjögren's syndrome differ in molecular signatures and treatment perspectives.Arthritis research & therapy · 2019Article
- Immunoglobulin G structure and rheumatoid factor epitopes.PloS one · 2019Article
- Structure-function analyses of a stereotypic rheumatoid factor unravel the structural basis for germline-encoded antibody autoreactivity.The Journal of biological chemistry · 2018Article
- Article
- Association between IgG4 Autoantibody and Complement Abnormalities in Systemic Lupus Erythematosus.Mediators of inflammation · 2016Article
- Human IgG4: a structural perspective.Immunological reviews · 2015Review
- Structural determinants of unique properties of human IgG4-Fc.Journal of molecular biology · 2014Article
- A rheumatoid factor paradox: inhibition of rituximab effector function.Arthritis research & therapy · 2013Article
- Isolation, characterization, and molecular modeling of a rheumatoid factor from a Hepatitis C virus infected patient with Sjögren's syndrome.TheScientificWorldJournal · 2013Article
- Experimental phasing using zinc anomalous scattering.Acta crystallographica. Section D, Biological crystallography · 2012Article
- B cell TLRs and induction of immunoglobulin class-switch DNA recombination.Frontiers in bioscience (Landmark edition) · 2012Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Rheumatoid factors (RF) are autoantibodies that recognize epitopes in the Fc region of immunoglobulin (Ig) G and that correlate with the clinical severity of rheumatoid arthritis (RA). Here we report the X-ray crystallographic structure, at 3 A resolution, of a complex between the Fc region of human IgG1 and the Fab fragment of a monoclonal IgM RF (RF61), derived from an RA patient and with a relatively high affinity for IgG Fc. In the complex, two Fab fragments bind to each Fc at epitopes close to the C terminus, and each epitope comprises residues from both Cgamma3 domains. A central role in the unusually hydrophilic epitope is played by the side-chain of Arg355, accounting for the subclass specificity of RF61, which recognizes IgG1,-2, and -3 in preference to IgG4, in which the corresponding residue is Gln355. Compared with a previously determined complex of a lower affinity RF (RF-AN) bound to IgG4 Fc, in which only residues at the very edge of the antibody combining site were involved in binding, the epitope bound by RF61 is centered in classic fashion on the axis of the V(H):V(L) beta-barrel. The complementarity determining region-H3 loop plays a key role, forming a pocket in which Arg355 is bound by two salt-bridges. The antibody contacts also involve two somatically mutated V(H) residues, reinforcing the suggestion of a process of antigen-driven maturation and selection for IgG Fc during the generation of this RF autoantibody.
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