Open AccessMonoclonal IgM rheumatoid factors bind IgG at a discontinuous epitope comprised of amino acid loops from heavy-chain constant-region domains 2 and 3.
Author(s) -
Steven E. Artandi,
Kathryn Calame,
Sherie L. Morrison,
Vincent R. Bonagura
Publication year - 1992
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.89.1.94
Subject(s) - epitope , epitope mapping , monoclonal antibody , amino acid , binding site , linear epitope , microbiology and biotechnology , chemistry , conformational epitope , immunoglobulin m , immunoglobulin light chain , immunoglobulin g , monoclonal , mutagenesis , rheumatoid factor , biochemistry , biology , antibody , mutation , immunology , gene
A combination of site-directed mutagenesis and exon exchange has been used to further define the structure on IgG recognized by monoclonal IgM rheumatoid factors (RFs) from patients with Waldenstrom macroglobulinemia. Most of these RFs bound IgG1, -2, and -4 but not IgG3. For these RFs, His-435 is a critical residue for binding and replacing it with arginine, the residue present in IgG3, destroys or reduces RF binding. However, additional polymorphic sequences in both the heavy-chain constant-region domains (CH) 2 and 3 are important for RF binding. Among the important residues in CH2 are amino acids 252-254 and 309-311, which are conserved among IgG isotypes and comprise two loops of amino acids on the surface of the domain. Therefore, at least three regions, two from CH2 and one from CH3, contribute significantly to the epitope recognized by the RFs. Although this epitope contains many of the same residues as the staphylococcal protein A binding site on IgG, the binding specificities of staphylococcal protein A and monoclonal RFs are not identical. Sera from patients with rheumatoid arthritis contain antibodies directed not only at this epitope but also at other sites on IgG.