Recognition characteristics of monoclonal antibodies that are cross-reactive with gangliosides and lipooligosaccharide from Campylobacter jejuni strains associated with Guillain-Barre and Fisher syndromes: Biochemistry

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TypeArticle
Journal titleBiochemistry
Volume46
Issue1
Pages3644; # of pages: 9
SubjectACID; Animals; Antibodies; Antibodies,Bacterial; Antibodies,Monoclonal; antibody; ANTIGEN; Antigens; Antigens,Bacterial; binding; Binding Sites; Binding Sites,Antibody; BINDING-SITE; Campylobacter; Campylobacter Infections; Campylobacter jejuni; Canada; chemistry; COMPONENT; Cross Reactions; DIFFERENCE; epitope; Epitopes; GANGLIOSIDE; Gangliosides; Guillain-Barre Syndrome; Humans; immunology; interaction; Kinetics; Ligands; lipooligosaccharide; Lipopolysaccharides; Magnetic Resonance Spectroscopy; Mice; Miller Fisher Syndrome; MONOCLONAL-ANTIBODIES; MONOCLONAL-ANTIBODY; N-Acetylneuraminic Acid; NMR; NMR spectroscopy; NMR-spectroscopy; oligosaccharide; Oligosaccharides; RATES; recognition; RESIDUES; RESONANCE; RESONANCES; Serum; SIGNALS; SITE; SITES; SPECTROSCOPY; STRAIN; STRAINS; structure; surface; Surface Plasmon Resonance; Syndrome; transfer
AbstractThe enteropathogen Campylobacter jejuni has the ability to synthesize glycan structures that are similar to mammalian gangliosides within the core component of its lipooligosaccharide (LOS). Exposure to ganglioside mimics in some individuals results in the production of autoantibodies that deleteriously attack nerve surface gangliosides, precipitating the onset of Guillain-Barre and Fisher syndromes (GBS and FS). We have characterized the interaction of four monoclonal antibodies (mAbs), established by sensitization of mice with LOS isolated from GBS- and FS-associated C. jejuni strains, with chemoenzymatically synthesized gangliooligosaccharides. Surface plasmon resonance (SPR) measurements demonstrate that three of the mAbs interact specifically with derivatives corresponding to their targeted gangliosides, with dissociation constants ranging from 10 to 20 microM. Antibody binding to the gangliooligosaccharides was probed by saturation transfer difference (STD) NMR spectroscopy. STD signals, resulting from antibody/oligosaccharide interaction, were observed for each of the four mAbs. In two cases, differential saturation transfer rates to oligosaccharide resonances enabled detailed epitope mapping. The binding of GD1a-S-Phe with GB1 is characterized by close association of the immunoglobulin with sites that are distributed over several residues of the oligosaccharide. This contrasts sharply with the profile observed for the binding of both GD3-S-Phe and GT1a-S-Phe with FS1. The close antigenic contacts in these ganglioside derivatives are confined to the N-acetylmannosaminyl portion of the terminal N-acetylneuraminic acid (NeuAc) residue of the disialosyl moiety. Our characterization of FS1 provides insight, at an atomic level, into how a single antigenic determinant presented by the LOS of C. jejuni can give rise to antibodies with binding promiscuity to [alphaNeuAc-(2-8)-alphaNeuAc]-bound epitopes and demonstrates why sera from FS patients have antibodies that are often reactive with more than one disialylated ganglioside
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedNo
NRC numberHOULISTON2007A
NPARC number9378324
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Record identifier4ca7b5f8-e87c-417e-8824-14685bf7bd03
Record created2009-07-10
Record modified2016-05-09
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