CHARACTERIZATION OF TERMINAL NEUNAC-ALPHA-2-3GAL-BETA-1-4GLCNAC SEQUENCE IN LIPOOLIGOSACCHARIDES OF NEISSERIA-MENINGITIDIS

Group B and C Neisseria meningitidis are the major cause of meningococ cal disease in the United States and in Europe, N.meningitidis lipooli gosaccharide (LOS), a major surface antigen, can be divided into 12 im munotypes of which L1 through L8 were found among Group B and C organi sms, Groups B and C but not Group A may sialylate their LOSs with N-ac etylneuraminic acid (NeuNAc) at the nonreducing end because they synth esize CMP-NeuNAc, Using sialic acid-galactose binding lectins as probe s in an ELISA format, six of the eight LOS immunotypes (L2, L3, L4, L5 , L7, and L8) in Groups B and C bound specifically to Maackia amurensi s leukoagglutinin (MAL), which recognizes NeuNAc alpha 2-3Gal beta 1-G lcNAc/Glc sequence, but not to Sambucus nigra agglutinin, which binds NeuNAc alpha 2-6Gal sequence, The combination of SDS-PAGE and MAL-blot analyses revealed that these six LOSs contained only the NeuNAc alpha 2-3Gal beta 1-4GlcNAc trisaccharide sequence in their 4.1 kDa LOS com ponents, which have a common terminal lacto-N-neotetraose (LNnT, Gal b eta 1-4GlcNAc beta 1-3Gal beta 1-4Glc) structure when nonsialylated as shown by previous studies. The LOS-lectin binding was abolished when the LOSs were treated with Newcastle disease viral neuraminidase which cleaves alpha 2-->3 linked sialic acid. Methylation analysis of a rep resentative LOS (L2) confirmed that NeuNAc is 2-->3 linked to Gal. Thu s, these LOSs structurally mimic certain glycolipids, i.e., paraglobos ide (LNnT-ceramide) and sialyl-paragloboside and some glycoproteins in having LNnT and N-acetyllactosamine sequences, respectively, with or without alpha 2-->3 linked NeuNAc, The molecular mimicry of the LOSs m ay play a role in the pathogenesis of N.meningitidis by assisting the organism to evade host immune defenses in man.