THE N-DOMAIN OF THE HUMAN CD66A ADHESION MOLECULE IS A TARGET FOR OPAPROTEINS OF NEISSERIA-MENINGITIDIS AND NEISSERIA-GONORRHOEAE

Using COS (African green monkey kidney) cells transfected with cDNAs e ncoding human cell surface molecules, we have identified human cellula r receptors for meningococcal virulence-associated Opa proteins, which are expressed by the majority of disease and carrier isolates. These receptors belong to the immunoglobulin superfamily of adhesion molecul es and are expressed on epithelial, endothelial and phagocytic cells, Using soluble chimeric receptor molecules, we have demonstrated that m eningococcal Opa proteins bind to the N-terminal domain of biliary gly coproteins (classified as BGP or CD66a) that belong to the CEA (CD66) family. Moreover, the Opa proteins of the related pathogen Neisseria g onorrhoeae, responsible for urogenital infections, also interact with this receptor, making CD66a a common target for pathogenic neisseriae. Over 95% of Opa-expressing clinical and mucosal isolates of meningoco cci and gonococci were shown to bind to the CD66 N-domain, demonstrati ng the presence of a conserved receptor-binding function in the majori ty of neisserial Opa proteins.