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Polysaccharide Processing and Presentation by the MHCII Pathway
Open accessAbstract
The adaptive immune system functions through the combined action of antigen-presenting cells (APCs) and T cells. Specifically, class I major histocompatibility complex antigen presentation to CD8(+) T cells is limited to proteosome-generated peptides from intracellular pathogens while the class II (MHCII) endocytic pathway presents only proteolytic peptides from extracellular pathogens to CD4(+) T cells. Carbohydrates have been thought to stimulate immune responses independently of T cells; however, zwitterionic polysaccharides (ZPSs) from the capsules of some bacteria can activate CD4(+) T cells. Here we show that ZPSs are processed to low molecular weight carbohydrates by a nitric oxide-mediated mechanism and presented to T cells through the MHCII endocytic pathway. Furthermore, these carbohydrates bind to MHCII inside APCs for presentation to T cells. Our observations begin to elucidate the mechanisms by which some carbohydrates induce important immunologic responses through T cell activation, suggesting a fundamental shift in the MHCII presentation paradigm.
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“PSA induces secretion of the potent anti-inflammatory cytokine IL-10 by CD4+ T cells and promotes the differentiation of naive CD4+ T cells into TH1 cells over TH2 cells.”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Cobb et al., 2004
In the citing paper
“The production of IL-10 is primarily mediated by DCs, which internalize PSA and present fragments to CD4+ T cells in conjunction with the major histocompatibility complex class II (MHC-II), thus stimulating activation and clonal expansion of T cells.”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Cobb et al., 2004
In the citing paper
“Importantly, PSA also activates toll-like receptor (TLR) 2 expressed on the surface of DCs, which triggers the release of cytokines that promote IL-10 production by T cells (Cobb et al., 2004; Dasgupta et al., 2014; Johnson et al., 2015; Mazmanian et al., 2005; 2008; Telesford et al., 2015; Q. Wang et al., 2006).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Cobb et al., 2004
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Metadata
- Authors
- Cobb, B. A., Wang, Q., Tzianabos, A. O., & Kasper, D. L.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Kasper, Dennis L
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2004-05
- Volume
- 117
- Issue
- 5
- Pages
- 677-687
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2917993
- OpenAlex
- W1988183869
- Cited by
- 340
- References
- 48
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 6 · 2023: 11 · 2022: 13 · 2021: 23 · 2020: 19 · 2019: 15 · 2018: 10 · 2017: 12 · 2016: 19 · 2015: 13 · 2014: 18 · 2013: 19 · 2012: 20
- FWCI
- 5.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI007061, AI52397, AI039576, R01AI039576, R01AI052397, T32AI007061)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- zwitterionic polysaccharides, MHC class II antigen presentation, nitric oxide, T cell activation, antigen-presenting cells, bacterial capsule, CD4+ T cells, endocytic pathway
- MeSH terms
- Animals, Antigen-Presenting Cells, Histocompatibility Antigens Class II, Endocytosis, Polysaccharides, Receptors, Antigen, T-Cell, T-Lymphocytes, Antigen Presentation, Mice
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