MEMBRANE COFACTOR PROTEIN (MCP OR CD46) IS A CELLULAR PILUS RECEPTOR FOR PATHOGENIC NEISSERIA

Pili of Neisseria gonorrhoeae and Neisseria meningitidis mediate bindi ng of the bacteria to human cell-surface receptors. We found that puri fied pili bound to a 55- to 60-kDa doublet band on SDS-PAGE of separat ed human epithelial cell extracts. This is a migration pattern typical of membrane cofactor protein (MCP or CD46). MCP is a widely distribut ed human complement regulatory protein. Attachment of the bacteria to epithelial cells was blocked by polyclonal and monoclonal antibodies d irected against MCP, suggesting that this complement regulator is a re ceptor for piliated Neisseria. We proved this hypothesis by demonstrat ing that piliated, but not non-piliated, gonococci bound to CHO cells transfected with human MCP-cDNA. We also demonstrated a direct interac tion between purified recombinant MCP and piliated Neisseria. Finally, recombinant MCP protein produced in E. coli inhibited attachment of t he bacteria to target cells. Taken together, our data show that MCP is a human cell-surface receptor for piliated pathogenic Neisseria.