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Cited by 340Immunotherapy and Immune ResponsesImmune Response and InflammationT-cell and B-cell Immunology

Polysaccharide processing and presentation by the MHCII pathway

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Cobb, Brian A, Wang, Qun, Tzianabos, Arthur O, Kasper, Dennis L·2004·Cell
DOI 10.1016/j.cell.2004.05.001PMC PMC2917993
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Abstract

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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Crossref · 10.1016/j.cell.2004.05.001

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  • PSA induces IL-10 secretion by CD4+ T cells and promotes differentiation of naive CD4+ T cells into TH1 over TH2 cells.

    “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

  • IL-10 production is primarily mediated by dendritic cells, which internalize PSA and present fragments to CD4+ T cells with MHC-II, stimulating activation and clonal expansion.

    “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

  • PSA activates TLR2 on dendritic cells, triggering release of cytokines that promote IL-10 production by T cells.

    “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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Authors
Cobb, B. A., Wang, Q., Tzianabos, A. O., & Kasper, D. L.
Affiliations
Brigham and Women's Hospital (US)
Corresponding author
Kasper, Dennis L
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2004-05
Volume
117
Issue
5
Pages
677-687
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2004.05.001
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
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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