CD66 RECEPTOR SPECIFICITY EXHIBITED BY NEISSERIAL OPA VARIANTS CONTROLLED BY PROTEIN DETERMINANTS IN CD66 N-DOMAINS

Neisseria gonorrhoeae strain MS11 is able to express 11 different opac ity (Opa) proteins on its outer surface. A number of these Opa protein s have been shown to function as adhesins through binding of CD66 rece ptors present on human cells. CD66 antigens, or carcinoembryonic antig en family members, constitute a family of glycoproteins belonging to t he immunoglobulin superfamily. Opa variants recognize this class of re ceptors in a differential manner such that certain Opa variants recogn ize up to four different CD66 receptors (CD66a, -c, -d, and -e), where as others recognize only two (CD66a and -e) or none. Ve explored the b asis for this receptor tropism in the present study. Our data show tha t glycoforms of CD66e and deglycosylated CD66e are recognized by gonoc occi in an Opa-specific manner. Binding by Opa variants of recombinant N-terminal domains of CD66 receptors expressed in Escherichia coli re flected the adherence specificities of Opa variants to HeLa cells expr essing native CD66 molecules. These data indicate that recognition of CD66 receptors by Opa variants is mediated by the protein backbone of the CD66 N-domains. Furthermore, by using chimeric constructs between different CD66 N-domains me identified distinct binding regions on the CD66e N-domain for specific groups of Opa variants, suggesting that t he differential recognition of CD66 receptors by Opa variants is dicta ted by the presence of specific binding regions on the N-domain of the receptor.