The unique solution structure and immunochemistry of the Candida albicans beta -1,2-mannopyranan cell wall antigens.
Synthetic oligomers of the antigenic Candida albicans (1-->2)-beta-mannopyranans adopt a compact solution conformation that leads to numerous inter-residue nuclear Overhauser effects, including unprecedented nuclear Overhauser effects between n and n + 3 residues. In excellent agreement with experimentally determined distances, unrestrained molecular dynamics point to a single family of conformations that approximate a compact helical motif with a three-residue repeat for this unique homopolymer. When the synthetic di- to hexasaccharides were employed as inhibitors of monoclonal antibodies, which protect mice against a lethal dose of the yeast pathogen, a novel pattern of inhibitor activity was observed. Instead of the paradigm first reported by Kabat (Kabat, E. A. (1962) Fed. Proc. 21, 694-701; Kabat, E. A. (1966) J. Immunol. 97, 1-11), wherein homo-oligosaccharides exhibit increasing inhibitory activity with increasing size, here the maximum activity is reached for di- and trisaccharides and diminishes significantly for tetra-, penta-, and hexasaccharides. These immunochemical data correlate with the ordered conformation of the beta-1,2-linked mannopyranan and imply that a uniquely small antigenic determinant has potential as a component of synthetic conjugate vaccines against Candida albicans.
Nitz
Mark
M
Department of Chemistry, the University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
Ling
Chang-Chun
CC
Otter
Albin
A
Cutler
Jim E
JE
Bundle
David R
DR
D000911:Antibodies, Monoclonal; D000946:Antigens, Fungal / Q000737:chemistry*; D002176:Candida albicans / Q000737:chemistry* / Q000276:immunology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002473:Cell Wall / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D006027:Glycosides / Q000032:analysis; D007150:Immunohistochemistry; D009682:Magnetic Resonance Spectroscopy; D008351:Mannans / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009844:Oligosaccharides
D000911:Antibodies, Monoclonal; D000946:Antigens, Fungal; D006027:Glycosides; D008351:Mannans; D009844:Oligosaccharides; C043364:beta-1,2-mannopyranan