The capsular polysaccharide of Neisseria meningitidis group C (MCPS) is a homopolymer of a(2--9) linked sialic acid. The polysaccharide is a thymus independent (TI) antigen which is poorly immunogenic in infants and young children. We showed earlier that the immune response to MCPS in BALB/c mice provides a model system which closely parallels the response to MCPS in man. Here we compare the BALB/c response to MCPS with that to an MCPS- tetanus toxoid(MCPS-TT) conjugate, a thymus dependent (TD) form of the antigen. The results indicate that MCPS-TT primed B cells have switched to produce IgG1 antibody by either MCPS, fixed whole bacteria or the covalent MCPS-TT. We have now generated a panel of 20 monoclonal antibodies (mAb) from mice immunized with MCPS-TT. Fifteen mAbs were from mice boosted with MCPS-TT, 13 are IgG1(k) and 2 are IgA(k). Three mAbs were from mice boosted with fixed bacteria and are IgG1(k). Two mAbs were from mice boosted with MCPS, one is IgG1(k) and the other is IgG2b(k). These antibodies are being purified and examined in detail for fine specificities using polysaccharides structurally related to MCPS. They will be further tested for bactericidal capacity because MCPS-TT immunization results in a large increase in serum bactericidal activity. The mAbs will be used to raise anti-idiotyppic antibodies which may provide serotypic markers of TI antibodies specific for MCPS. These mAbs will be used to examine whether TI and TD forms of polysaccharides stimulate the same antibody forming cells. Finally, in order to examine differences in affinity maturation between the TI and TD forms of the antigen, we will measure and compare the affinities between the anti-MCPS and the anti-MCPS-TT mAbs.
