Structural and immunochemical characterization of a Neisseria gonorrhoeae epitope defined by a monoclonal antibody 2C7; the antibody recognizes a conserved epitope on specific lipo-oligosaccharides in spite of the presence of human carbohydrate epitopes

Lipo-oligosaccharides (LOS) produced by Neisseria gonorrhoeae are important antigenic and immunogenic components of the outer membrane complex. Previo usly, we showed that murine monoclonal antibody (mAb) 2C7 did not cross-rea ct with human glycosphingolipids but identified the LOS epitope that is wid ely expressed in vivo and in vitro (Gulati, S., McQuillen, D. P., Mandrell, R. E., Jani, D. E,, and Rice, P. A. (1996) J. Infect. Dis. 174, 1223-1237) . In the present study, we analyzed the structure of gonococcal strain WG L OS containing the 2C7 epitope and investigated the structural requirements for expression of the epitope, We determined that the WG LOS components are Hep[1]-elongated forms of 15253 LOS that have a lactose on both Hep[1] and Hep[2] (Yamasaki, a, Kerwood, D. E., Schneider, H., Quinn, a P., Griffiss, J. M., and Mandrell, a E, (1994) J. Biol. Chem. 269, 30345-30351). In addi tion, we found that expression of the 2C7 epitope within the LOS is blocked when the Hep[2]-lactose is elongated. Eased on the structural data of thes e LOS and the results obtained from immunochemical analyses, we conclude th e following: 1) mAb 2C7 requires both the 15253 OS minimum structure and th e N-linked fatty acids in the lipoidal moiety for expression of the epitope ; 2) mAb 2C7 binds to the LOS that elongates the lactose on Hep[1] of the 1 5253 OS, but not the one on Hep[2]; and 3) the 2C7 epitope is expressed on gonococcal LOS despite the presence of human carbohydrate epitopes such as a lactosamine or its N-acetylgalactosaminylated (globo) form. Our study sho ws that the conserved epitope defined by mAb 2C7 could potentially be used as a safe site for the development of a vaccine candidate.