ArticleGlycobiology2008
Characteristics of carbohydrate antigen binding to the presentation protein HLA-DR.
Article in Glycobiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 70 citations in OpenAlex.
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- Recent advances on smart glycoconjugate vaccines in infections and cancer.The FEBS journal · 2022Review
- Microbiota Signals during the Neonatal Period Forge Life-Long Immune Responses.International journal of molecular sciences · 2021Review
- Natural and synthetic carbohydrate-based vaccine adjuvants and their mechanisms of action.Nature reviews. Chemistry · 2021Review
- Human T cell glycosylation and implications on immune therapy for cancer.Human vaccines & immunotherapeutics · 2020Review
- Synthetic, Zwitterionic Sp1 Oligosaccharides Adopt a Helical Structure Crucial for Antibody Interaction.ACS central science · 2019Article
- Classical and novel strategies to develop aHuman vaccines & immunotherapeutics · 2019Review
- Chemical Synthesis of Rare, Deoxy-Amino Sugars Containing Bacterial Glycoconjugates as Potential Vaccine Candidates.Molecules (Basel, Switzerland) · 2018Review
- The Gut Microbiome and Multiple Sclerosis.Cold Spring Harbor perspectives in medicine · 2018Review
- The influence of gut-derived CD39 regulatory T cells in CNS demyelinating disease.Translational research : the journal of laboratory and clinical medicine · 2017Review
- Carbohydrates as T-cell antigens with implications in health and disease.Glycobiology · 2016Review
- Dendritic cell-specific Mgat2 knockout mice show antigen presentation defects but reveal an unexpected CD11c expression pattern.Glycobiology · 2016Article
- The interplay between microbiota and inflammation: lessons from peritonitis and sepsis.Clinical & translational immunology · 2016Review
- Physical Interaction of T Cells with Dendritic Cells Is Not Required for the Immunomodulatory Effects of the Edible MushroomFrontiers in immunology · 2016Article
- In vivo imaging and tracking of host-microbiota interactions via metabolic labeling of gut anaerobic bacteria.Nature medicine · 2015Article
- Bacterial capsular polysaccharide prevents the onset of asthma through T-cell activation.Glycobiology · 2015Article
- Polysaccharide A from the capsule of Bacteroides fragilis induces clonal CD4+ T cell expansion.The Journal of biological chemistry · 2015Article
- Mgat2 ablation in the myeloid lineage leads to defective glycoantigen T cell responses.Glycobiology · 2014Article
- Tumor-Associated Glycans and Immune Surveillance.Vaccines · 2013Review
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Zwitterionic polysaccharide antigens (ZPSs) were recently shown to activate T cells in a class II major histocompatibility complex (MHCII)-dependent fashion requiring antigen presenting cell (APC)-mediated oxidative processing although little is known about the mechanism or affinity of carbohydrate presentation (Cobb BA, Wang Q, Tzianabos AO, Kasper DL. 2004. Polysaccharide processing and presentation by the MHCII pathway. Cell. 117:677-687). A recent study showed that the helical conformation of ZPSs (Wang Y, Kalka-Moll WM, Roehrl MH, Kasper DL. 2000. Structural basis of the abscess-modulating polysaccharide A2 from Bacteroides fragilis. Proc Natl Acad Sci USA. 97:13478-13483; Choi YH, Roehrl MH, Kasper DL, Wang JY. 2002. A unique structural pattern shared by T-cell-activating and abscess-regulating zwitterionic polysaccharides. Biochemistry. 41:15144-15151) is closely linked with immunogenic activity (Tzianabos AO, Onderdonk AB, Rosner B, Cisneros RL, Kasper DL. 1993. Structural features of polysaccharides that induce intra-abdominal abscesses. Science. 262:416-419) and is stabilized by a zwitterionic charge motif (Kreisman LS, Friedman JH, Neaga A, Cobb BA. 2007. Structure and function relations with a T-cell-activating polysaccharide antigen using circular dichroism. Glycobiology. 17:46-55), suggesting a strong carbohydrate structure-function relationship. In this study, we show that PSA, the ZPS from Bacteroides fragilis, associates with MHCII at high affinity and 1:1 stoichiometry through a mechanism mirroring peptide presentation. Interestingly, PSA binding was mutually exclusive with common MHCII antigens and showed significant allelic differences in binding affinity. The antigen exchange factor HLA-DM that catalyzes peptide antigen association with MHCII also increased the rate of ZPS association and was required for APC presentation and ZPS-mediated T cell activation. Finally, the zwitterionic nature of these antigens was required only for MHCII binding, and not endocytosis, processing, or vesicular trafficking to MHCII-containing vesicles. This report is the first quantitative analysis of the binding mechanism of carbohydrate antigens with MHCII and leads to a novel model for nontraditional MHCII antigen presentation during bacterial infections.
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