Murine immune response to the Neisseria meningitidis group C capsular polysaccharide. II. Specificity.

As a means of further understanding the regulation of diversity and the development of protective immunity to the Neisseria meningitidis group C capsular polysaccharide (MCPS), we have generated and characterized, in detail, a panel of mAb against MCPS, a homopolymer of alpha(2----9)-sialic acid. Whereas the serum response to MCPS is restricted to the IgM and IgG3 isotypes, the panel of mAb includes, in addition, both IgG1 and IgG2b. Among 15 mAb of four isotypes, seven different specificities were observed based on direct binding in a fluorescence ELISA and precipitation in gel. Although all the mAb were derived from mice immunized with bacteria encapsulated with the native MCPS (strain C11), only 7 of 15 reacted with MCPS alone. Seven of 15 reacted with a natural O-acetyl-negative variant (OAc-, strain MC19) polysaccharide as well as with MCPS. Five of these reacted as much as 3 logs better with OAc- than MCPS and the other two reacted better with MCPS than OAc-. One mAb appeared to be alpha(2----9)-linkage specific as it reacted not only with MCPS and OAc-, but also with the capsular polysaccharide of Escherichia coli K92, a polymer of sialic acid linked alternately alpha(2----8) and alpha(2----9). None of the mAb reacted with the capsular polysaccharide of E. coli K1, a homopolymer of alpha(2----8)-sialic acid. In general, there was a good correlation between the ability to precipitate Ag in gel and to agglutinate bacteria; however, 3 of 15 mAb, all IgG3, did not conform to this rule in that they precipitated Ag but did not agglutinate bacteria of the relevant capsular specificity. Antibodies of both IgM and IgG isotypes and of both major specificities, MCPS-specific and those binding MCPS and OAc-, were bactericidal for strain C11, whereas only those reactive with OAc- were able to kill strain MC19.