Molecular analysis of monoclonal antibodies to group variant capsular polysaccharide of Neisseria meningitidis: recurrent heavy chains and alternative light chain partners.

We determined the molecular sequence of monoclonal antibodies (mAbs) to serogroups B and C capsular polysaccharides (PS) of Neisseria meningitidis. N. meningitidis infections are a leading cause of bacterial septicemia and meningitis in humans. Antibodies to PS are fundamental to host defense and diagnostics. The polysaccharide capsule of group B N. meningitidis is poorly immunogenic and thus is an important model for studying pathogen-host co-evolution through understanding the molecular basis of the host immune response. We used a modified reverse-transcriptase PCR to amplify and sequence the V-genes of murine hybridomas produced against types B and C capsular PS. Databank analysis of the sequences encoding the V-genes of type C capsular PS mAb, 4-2-C, reveal that heavy chain alleles are recurrently used to encode this specificity in mice. Interestingly, a V-gene from the same germline family also encodes the V-domain of mAbs 2-2-B, which targets the antigenically distinct serogroup B capsular PS. Somatic mutation, junctional diversity and alternative light chains collectively impart the specificity for these serologically distinct epitopes. Knowledge of the specific immunoglobulin genes used to target common bacterial virulence factors may lead to insights on pathogen-host co-evolution, and the potential use of this information in pre-symptomatic diagnosis is discussed.