title: Structural characterization and MHCII-dependent immunological properties of the zwitterionic O-chain antigen of Morganella morganii.
abstract: Morganella morganii is a commensal Gram-negative bacterium that has long been known to produce an antigen bearing phosphocholine groups. We determined the structure of this O-chain antigen and found that its repeating unit also contains a free amino group and a second phosphate: This alternating charge character places the M. morganii O-chain polysaccharide into a small family of zwitterionic polysaccharides (ZPSs) known to induce T-cell-dependent immune responses via presentation by class II major histocompatibility complex (MHCII) molecules. In vitro binding assays demonstrate that this O-chain interacts with MHCII in a manner that competes with binding of the prototypical ZPS antigen PSA from Bacteroides fragilis, despite its lack of a helical structure. Cellular studies also showed that the M. morganii polysaccharide induces activation of CD4(+) T-cells. Antibody binding experiments using acid hydrolyzed fragments representing the monomer and higher oligomers of the repeating unit showed that the phosphocholine group was the dominant element of the epitope with an overall affinity (K(D)) of about 5 × 10(-5) M, a typical value for an IgM anti-carbohydrate antibody but much lower than the affinity for phosphocholine itself. These data show that the structure of the M. morganii polysaccharide contains a unique zwitterionic repeating unit which allows for immune recognition by T-cells, making it the first identified T-cell-dependent O-chain antigen.
authors.affiliation: Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ont., Canada K1A 0R6. martin.young@nrc-cnrc.gc.ca
authors.forename: N Martin
authors.initials: NM
authors.lastname: Young
authors.forename: Lori S C
authors.initials: LS
authors.lastname: Kreisman
authors.forename: Jacek
authors.initials: J
authors.lastname: Stupak
authors.forename: Leann L
authors.initials: LL
authors.lastname: MacLean
authors.forename: Brian A
authors.initials: BA
authors.lastname: Cobb
authors.forename: James C
authors.initials: JC
authors.lastname: Richards
mesh_terms: D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D007477:Ions; D007700:Kinetics; D020613:Morganella morganii / Q000276:immunology* / Q000378:metabolism; D019081:O Antigens / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000949:Histocompatibility Antigens Class II; D007477:Ions; D019081:O Antigens