MEMBRANE COFACTOR PROTEIN (CD46) IS A KERATINOCYTE RECEPTOR FOR THE M-PROTEIN OF THE GROUP-A STREPTOCOCCUS

The pathogenic Gram-positive bacterium Streptococcus pyogenes (group A streptococcus) is the causative agent of numerous suppurative disease s of human skin, The M protein of S. pyogenes mediates the adherence o f the bacterium to keratinocytes, the most numerous cell type in the e pidermis, In this study, we have constructed and analyzed a series of mutant M proteins and have shown that the C repeat domain of the M mol ecule is responsible for cell recognition, The binding of factor H, a serum regulator of complement activation, to the C repeat region of M protein blocked bacterial adherence. Factor H is a member of a large f amily of complement regulatory proteins that share a homologous struct ural motif termed the short consensus repeat, Membrane cofactor protei n (MCP), or CD46, is a short consensus repeat-containing protein found on the surface of keratinocytes, and purified MCP could competitively inhibit the adherence of S. pyogenes to these cells, Furthermore, the M protein was found to bind directly to MCP, whereas mutant M protein s that lacked the C repeat domain did not bind MCP, suggesting that re cognition of MCP plays an important role in the ability of the strepto coccus to adhere to keratinocytes.