A unique structural pattern shared by T-cell-activating and abscess-regulating zwitterionic polysaccharides.
In contrast to the conventional dogma that carbohydrates are poorly immunogenic T-cell-independent antigens, zwitterionic polysaccharides (ZPSs) can significantly stimulate T-cell proliferation and regulate abscess formation in bacterial infection. Despite their similar biological activities, ZPSs from various bacteria are greatly different in primary chemical compositions and building block linkages. To identify the common structural features that govern the peculiar immunologic activity of ZPSs, we have been determining three-dimensional structures of compositionally different ZPSs by NMR spectroscopy and molecular mechanics and dynamics calculations. We report here the conformation of type 1 capsular polysaccharide from the human pathogen Streptococcus pneumoniae (Sp1) to be a right-handed helix with repeated zwitterionically charged grooves. We also report the striking similarity between the structures of Sp1 and our previously determined PS A2 from Bacteroides fragilis. These results support our hypothesis that T-cell-activating ZPSs assume similar conformational and charge patterns that are recognized by specific receptors and that account for their common property as T-cell activators.
Choi
Yong-Hoon
YH
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Roehrl
Michael H
MH
Kasper
Dennis L
DL
Wang
Julia Y
JY
D000038:Abscess / Q000382:microbiology*; D016667:Bacterial Capsules / Q000737:chemistry*; D002236:Carbohydrate Conformation; D003198:Computer Simulation; D006801:Humans; D007477:Ions; D008213:Lymphocyte Activation; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D055672:Static Electricity; D013296:Streptococcus pneumoniae / Q000737:chemistry* / Q000472:pathogenicity; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000382:microbiology*; D013816:Thermodynamics
D007477:Ions