The deficient cleavage of M protein-bound IgG by IdeS: Insight into the escape of Streptococcus pyogenes from antibody-mediated immunity
Date of Original Version
IdeS (IgG-degrading enzyme of Streptococcus pyogenes) is a virulence factor for S. pyogenes, group A Streptococcus (GAS). IdeS is believed to allow GAS to evade antibody-mediated phagocytosis by cleaving IgG at the lower hinge region. Human immunoglobulins bind to the GAS surface by two mechanisms: Specific antibodies attach at the Fab region to their specific antigens on the bacterial surface. Immunoglobulins can also attach nonspecifically at the Fc region to streptococcal M and M-like proteins. This phenomenon is believed to form the host-like coat and to block the recognition of Fc region by Fc receptor on phagocytes and antibody-dependent cell-mediated cytotoxicity. It is not known whether IdeS preferentially cleaves IgG attached at the Fab or Fc regions. To explore this issue, we used Sepharose beads coated with protein A or L or M protein as surrogate markers for specific (Fab) and nonspecific (Fc) binding sites. We found that IdeS cleaved Fab-bound IgG as rapidly as soluble IgG. In contrast, Fc-bound IgG was cleaved about 4 fold less than soluble IgG. In a competitive binding assay, we found that M protein had a greater affinity than IdeS to attach to the Fc region of human IgG. Thus, IdeS exhibited preferential IgG endopeptidase activity for Fab-bound IgG while allowing the non-specific binding of IgG to remain attached to M protein. We propose that this preferential enzymatic activity accounts for the ability of GAS to resist immunoglobulin-mediated phagocytosis and cytotoxicity. © 2011 Elsevier Ltd.
Publication Title, e.g., Journal
Su, Yu Fang, Woei Jer Chuang, Shih Min Wang, Wen Yi Chen, Chuan Chiang-Ni, Yee Shin Lin, Jiunn Jong Wu, and Ching Chuan Liu. "The deficient cleavage of M protein-bound IgG by IdeS: Insight into the escape of Streptococcus pyogenes from antibody-mediated immunity." Molecular Immunology 49, 1-2 (2011): 134-142. doi: 10.1016/j.molimm.2011.08.002.