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

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 γ-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 β-grasp C-terminal domain of SSL10 (SSL1095–197) 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 FcγRs on monocytes and neutrophil phagocytosis of IgG1-opsonized bacteria. Mutagenesis of human IgG1 at key sites significantly reduced SSL10 binding including Lys322 that is important for C1q binding, a combination of Leu234 and Leu235 that are important for FcγR binding, and a combination of Lys274 and Asp276 that together are unique to IgG1. These mutations suggest that the most likely site bound by SSL10 is the outer face of the Cγ2 domain in close proximity to both the FcγR and C1q binding sites. SSL10 is a potential virulence factor for S. aureus targeting IgG1-mediated immunity.