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

Authors

Yu Fang Su, National Cheng Kung University College of Medicine
Woei Jer Chuang, National Cheng Kung University College of Medicine
Shih Min Wang, National Cheng Kung University College of Medicine
Wen Yi Chen, National Cheng Kung University College of Medicine
Chuan Chiang-Ni, National Cheng Kung University College of Medicine
Yee Shin Lin, National Cheng Kung University College of Medicine
Jiunn Jong Wu, National Cheng Kung University College of Medicine
Ching Chuan Liu, National Cheng Kung University Hospital

Document Type

Article

Date of Original Version

10-1-2011

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. © 2011 Elsevier Ltd.

Publication Title, e.g., Journal

Molecular Immunology

Volume

49

Issue

1-2

Citation/Publisher Attribution

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.