The deficient cleavage of M protein-bound IgG by IdeS: Insight into the escape of Streptococcus pyogenes from antibody-mediated immunity

Yu Fang Su, Woei Jer Chuang, Shih Min Wang, Wen Yi Chen, Chuan Chiang-Ni, Yee Shin Lin, Jiunn Jong Wu, Ching Chuan Liu

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)134-142
Number of pages9
JournalMolecular Immunology
Volume49
Issue number1-2
DOIs
Publication statusPublished - 2011 Oct 1

All Science Journal Classification (ASJC) codes

  • Immunology
  • Molecular Biology

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