Publication

Molecular recognition ofcandida albicans(1→2)-β-mannan oligosaccharides by a protective monoclonal antibody reveals the immunodominance of internal saccharide residues

Johnson, Margaret A.
Cartmell, Jonathan
Weisser, Nina E.
Woods, Robert J.
Bundle, David R.
Citation
Johnson, Margaret A. Cartmell, Jonathan; Weisser, Nina E.; Woods, Robert J.; Bundle, David R. (2012). Molecular recognition ofcandida albicans(1→2)-β-mannan oligosaccharides by a protective monoclonal antibody reveals the immunodominance of internal saccharide residues. Journal of Biological Chemistry 287 (22), 18078-18090
Abstract
A self-consistent model of beta-mannan oligosaccharides bound to a monoclonal antibody, C3.1, that protects mice against Candida albicans has been developed through chemical mapping, NMR spectroscopic, and computational studies. This antibody optimally binds di- and trisaccharide epitopes, whereas larger oligomers bind with affinities that markedly decrease with increasing chain length. The (1 -> 2)-beta-linked di-, tri-, and tetra-mannosides bind in helical conformations similar to the solution global minimum. Antibody recognition of the di- and trisaccharide is primarily dependent on the mannose unit at the reducing end, with the hydrophobic face of this sugar being tightly bound. Recognition of a tetrasaccharide involves a frameshift in the ligand interaction, shown by strong binding of the sugar adjacent to the reducing end. We show that frameshifting may also be deliberately induced by chemical modifications. Molecular recognition patterns similar to that of mAb C3.1, determined by saturation transfer difference-NMR, were also observed in polyclonal sera from rabbits immunized with a trisaccharide glycoconjugate. The latter observation points to the importance of internal residues as immunodominant epitopes in (1 -> 2)-beta-mannans and to the viability of a glycoconjugate vaccine composed of a minimal length oligosaccharide hapten.
Funder
Publisher
American Society for Biochemistry & Molecular Biology (ASBMB)
Publisher DOI
10.1074/jbc.m112.355578
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland