VARIABLE REGION SEQUENCES AND IDIOTYPIC EXPRESSION OF A PROTECTIVE HUMAN-IMMUNOGLOBULIN M-ANTIBODY TO CAPSULAR POLYSACCHARIDES OF NEISSERIA-MENINGITIDIS GROUP-B AND ESCHERICHIA-COLI K1

We determined the heavy (H)- and light L-chain variable (V) region nuc leotide and translated amino acid sequences of the human immunoglobuli n M(kappa) monoclonal antibody (MAb) 5E1, which is specific for the po lysaccharide capsule of Escherichia coli K1 and Neisseria meningitidis group B (poly[alpha(2-->8)-N-acetylneuraminic acid]) and which is pro tective in animal models of infection. The 5E1 V-H gene is a member of the V(H)IIIb family and is 97% homologous to the 9.1 germ line gene. The 5E1 V-L gene is a member of the kappa I subgroup and is 98% homolo gous to the germ line gene, 15A, also known as KL012. The V-L and/or V -H genes used by 5E1 are highly homologous to the V genes encoding ant ibodies to the Haemophilus influenzae type b polysaccharide and to ant ibodies reactive with self-antigens such as erythrocyte ''i,'' DNA, an d thyroid peroxidase. We also produced three murine anti-idiotype (Id) MAbs against 5E1. All three anti-Ids recognize a minor subset of anti meningococcal B polysaccharide antibodies present in serum from normal adults. Two of the anti-Ids define distinct Ids associated with antib odies having kappa I-15A V regions. These 15A-associated Ids are expre ssed by some heterologous human antimeningococcal B polysaccharide MAb s, and they also are independently expressed by two human MAbs that ar e specific for either the H. influenzae b polysaccharide or the i eryt hrocyte antigen and that utilize the kappa I-I5A V region. Taken toget her, these data indicate that the 5E1 antibody uses V regions that rec ur in the human antibody repertoires to this polysaccharide and to str ucturally dissimilar polysaccharides and autoantigens. Thus, the poor immunogenicity of poly[alpha(2-->8)-N-acetylneuraminic acid] cannot be explained by the unavailability of certain critical V-H and V-L genes required for generation of antibody response.