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Recognition of IgG‐Derived Peptides by a Human IgM with an Unusual Combining Site
Author(s) -
Yuriev E.,
Ramsland P. A.,
Edmundson A. B.
Publication year - 2002
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.0300-9475.2002.01032.x
Subject(s) - immunoglobulin light chain , binding site , fragment crystallizable region , peptide , antibody , chemistry , rheumatoid factor , immunoglobulin g , binding selectivity , complementarity determining region , docking (animal) , microbiology and biotechnology , biology , biochemistry , genetics , medicine , nursing
A monoclonal immunoglobulin (Ig)M cryoglobulin (Mez) with interesting binding behaviour was isolated from a Waldenström's macroglobulinemia (WM) patient. It demonstrated very strong binding to peptides derived from the sequences of human IgG. However, when tested for binding to intact IgG, this antibody (Ab) did not show any rheumatoid factor (RF) activity. We propose several nonexclusive structural interpretations of the Mez‐binding propensities, based on the orientations and solvent accessibilities of ligand residues and the nature of the Ab‐binding site. To further characterize the structural features of Mez‐peptide binding, IgG‐derived octapeptides were docked into the Mez fragment variable (Fv)‐binding site, revealing additional reasons for Mez‐binding selectivity based on the interactions of the docked peptides with the Mez Fv. The problem was also approached from an immunological perspective. Comparisons of Mez variable region of the light chain (VL)/variable region of the heavy chain (VH) sequences with those of human germlines and known IgM RFs allowed us to provide a possible outline tracing the structural and functional origins of the Mez IgM. Coupled with examinations of interactions in docked complexes, this analysis led us to propose that the potential for RF activity, demonstrated through Mez binding to IgG‐derived peptides, was owing to the inherent sequence and structure of the Mez IgM, rather than to somatic mutations. Thus, Mez IgM may occupy an intermediate niche between IgMs with and without RF activity.