A common theme in interaction of bacterial immunoglobulin-binding proteins with immunoglobulins illustrated in the equine system

Melanie J. Lewis, Mary Meehan, Peter Owen, Jennifer M. Woof (Lead / Corresponding author)

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    Abstract

    The M protein of Streptococcus equi subsp. equi known as fibrinogen-binding protein (FgBP) is a cell wall-associated protein with antiphagocytic activity that binds IgG. Recombinant versions of the seven equine IgG subclasses were used to investigate the subclass specificity of FgBP. FgBP bound predominantly to equine IgG4 and IgG7, with little or no binding to the other subclasses. Competitive binding experiments revealed that FgBP could inhibit the binding of staphylococcal protein A and streptococcal protein G to both IgG4 and IgG7, implicating the Fc interdomain region in binding to FgBP. To identify which of the two IgG Fc domains contributed to the interaction with FgBP, we tested two human IgG1/IgA1 domain swap mutants and found that both domains are required for full binding, with the CH3 domain playing a critical role. The binding site for FgBP was further localized using recombinant equine IgG7 antibodies with single or double point mutations to residues lying at the CH2-CH3 interface. We found that interaction of FgBP with equine IgG4 and IgG7 was able to disrupt C1q binding and antibody-mediated activation of the classical complement pathway, demonstrating an effective means by which S. equi may evade the immune response. The mode of interaction of FgBP with IgG fits a common theme for bacterial Ig-binding proteins. Remarkably, for those interactions studied in detail, it emerges that all the Ig-binding proteins target the CH2-CH3 domain interface, regardless of specificity for IgG or IgA, streptococcal or staphylococcal origin, or host species (equine or human).

    Original languageEnglish
    Pages (from-to)17615-17623
    Number of pages9
    JournalJournal of Biological Chemistry
    Volume283
    Issue number25
    DOIs
    Publication statusPublished - 20 Jun 2008

    Keywords

    • FC-ALPHA-RI
    • STREPTOCOCCUS-EQUI
    • SUBSP EQUI
    • FIBRINOGEN-BINDING
    • STAPHYLOCOCCUS-AUREUS
    • COMPLEMENT ACTIVATION
    • CLASSICAL PATHWAY
    • MUCOSAL ANTIBODY
    • IMMUNE-RESPONSES
    • IGG SUBCLASSES

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