Specificity of Staphylococcal Superantigen-Like Protein 10 Toward the Human IgG1 Fc Domain

J Immunol. 2010 Jun 1;184(11):6283-92. doi: 10.4049/jimmunol.0903311. Epub 2010 Apr 28.

Abstract

Staphylococcal superantigen-like protein 10 (SSL10) is a highly conserved member of the SSL family secreted by Staphylococcus aureus that displays structural but not functional similarity to superantigens. SSL10 bound to fibrinogen and fibronectin from plasma and in addition displayed striking specificity toward the gamma-1 subclass of human Igs. SSL10 also bound strongly to primate IgG but not to any other species tested, including rabbit, pig, guinea pig, cow, sheep, or mouse. A soluble form of the 12-kDa beta-grasp C-terminal domain of SSL10 (SSL10(95-197)) retained fibrinogen and fibronectin binding but lost the ability to bind IgG1, indicating that SSL10 bound to IgG1 primarily through its N-terminal oligonucleotide binding fold domain. SSL10 blocked the binding of IgG1 to FcgammaRs on monocytes and neutrophil phagocytosis of IgG1-opsonized bacteria. Mutagenesis of human IgG1 at key sites significantly reduced SSL10 binding including Lys(322) that is important for C1q binding, a combination of Leu(234) and Leu(235) that are important for FcgammaR binding, and a combination of Lys(274) and Asp(276) that together are unique to IgG1. These mutations suggest that the most likely site bound by SSL10 is the outer face of the Cgamma2 domain in close proximity to both the FcgammaR and C1q binding sites. SSL10 is a potential virulence factor for S. aureus targeting IgG1-mediated immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibody Specificity / immunology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Bacterial Proteins / metabolism
  • Blotting, Western
  • Cattle
  • Cell Separation
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Guinea Pigs
  • Humans
  • Immunoglobulin Fc Fragments / immunology
  • Immunoglobulin Fc Fragments / metabolism*
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism*
  • Immunoprecipitation
  • Mice
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Rabbits
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Staphylococcus aureus / immunology*
  • Staphylococcus aureus / metabolism
  • Staphylococcus aureus / pathogenicity
  • Superantigens / genetics
  • Superantigens / immunology*
  • Superantigens / metabolism
  • Virulence Factors

Substances

  • Bacterial Proteins
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Superantigens
  • Virulence Factors