DIFFERENTIAL OPA SPECIFICITIES FOR CD66 RECEPTORS INFLUENCE TISSUE INTERACTIONS AND CELLULAR-RESPONSE TO NEISSERIA-GONORRHOEAE

The ability of all 11 variable opacity (Opa) proteins encoded by Neiss eria gonorrhoeae MS11 to interact directly with the five CD66 antigens was determined. Transfected HeLa cell lines expressing individual CD6 6 antigens were infected with recombinant N. gonorrhoeae and Escherich ia coli strains expressing defined Opas. Based upon the ability of the se bacteria to bind and invade and to isolate specifically CD66 antige ns from detergent-soluble extracts of the corresponding cell lines, di stinct specificity groups of Opa interaction with CD66 were seen. Defi ning these specificity groups allowed us to assign a specific function for CD66a in the Opa-mediated interaction of gonococci with two diffe rent target cell types, which are both known to co-express multiple CD 66 antigens. The competence of individual Opas to interact with CD66a was strictly correlated with their ability to induce an oxidative resp onse by polymorphonuclear neutrophils. The same Opa specificity was ob served for the level of gonococcal binding to primary endothelial cell s after stimulation with TNF alpha, which was shown to increase the ex pression of CD66a rather than CD66e. As CD66e alone is expressed on ot her target tissues of gonococcal pathogenicity, Opa variation probably contributes to the cell tropism displayed by gonococci.