IG-BINDING SURFACE-PROTEINS OF STREPTOCOCCUS-PYOGENES ALSO BIND HUMANC4B-BINDING PROTEIN (C4BP), A REGULATORY COMPONENT OF THE COMPLEMENT-SYSTEM

Streptococcus pyogenes, an important human pathogen, expresses several proteins that interact with the immune system of the host. Among the proteins isolated from different bacterial strains are antiphagocytic M proteins, Ig Fc-binding proteins and exotoxins that act as superanti gens. Here we report a novel interaction between S. pyogenes and the h uman immune system, the ability of most S. pyogenes strains to bind hu man C4BP (C4b-binding protein), a 570-kDa serum protein that inhibits the classical pathway of complement activation. Molecular analysis of three different streptococcal strains demonstrated that C4BP binds to protein Arp or protein Sir, two Ig-binding cell surface molecules that are members of the M protein family. These bacterial proteins have se parate high affinity binding sites for Ig and for C4BP, as demonstrate d by inhibition tests and binding assays with purified components. A s ingle streptococcal cell surface molecule, Arp or Sir, therefore combi nes the abilities to bind Ig and C4BP, two high m.w. components of the immune system. Two bacterial strains expressing Arp or Sir were shown to selectively bind C4BP in whole human serum, suggesting that S. pyo genes also binds C4BP in the infected host. When bound to streptococca l cells, C4BP retained its ability to act as a cofactor in the degrada tion of C4b by factor I. These results indicate that many strains of S . pyogenes interfere with the classical pathway of complement activati on by binding C4BP to the bacterial cell surface.