Polysaccharide A from the capsule of Bacteroides fragilis induces clonal CD4+ T cell expansion
Open accessAbstract
For 3 decades, the view of MHCII-dependent antigen presentation has been completely dominated by peptide antigens despite our 2004 discovery in which MHCII was shown to present processed fragments of zwitterionic capsular polysaccharides to T cells. Published findings further demonstrate that polysaccharide A (PSA) from the capsule of Bacteroides fragilis is a potent activator of CD4(+) T cells and that these T cells have important biological functions, especially in the maintenance of immunological homeostasis. However, little is known about the nature of T cell recognition of the polysaccharide-MHCII complex or the phenotype of the resulting activated cells. Here, we use next-generation sequencing of the αβT cell receptor of CD4(+) T cells from mice stimulated with PSA in comparison with protein antigen simulation and non-immunized controls and found that PSA immunization induced clonal expansion of a small subset of suppressive CD4(+)CD45RB(low) effector/memory T cells. Moreover, the sequences of the complementarity-determining region 3 (CDR3) loop from top clones indicate a lack of specific variable β and joining region use and average CDR3 loop length. There was also a preference for a zwitterionic motif within the CDR3 loop sequences, aligning well with the known requirement for a similar motif within PSA to enable T cell activation. These data support a model in which PSA, and possibly other T cell-dependent polysaccharide antigens, elicits a clonal and therefore specific CD4(+) T cell response often characterized by pairing dual-charged CDR3 loop sequences with dual-charged PSA.
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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 Johnson et al., 2015
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- Authors
- Johnson, J. L., Jones, M. B., & Cobb, B. A.
- Affiliations
- Case Western Reserve University (US)
- Corresponding author
- Cobb, Brian A.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 290
- Issue
- 8
- Pages
- 5007-5014
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC4335237
- OpenAlex
- W2026779719
- Cited by
- 74
- References
- 27
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 12 · 2020: 6 · 2019: 9 · 2018: 5 · 2017: 7 · 2016: 4 · 2015: 2
- FWCI
- 1.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (GM082916, OD004225)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- polysaccharide A, Bacteroides fragilis, capsular polysaccharide, CD4+ T cells, T cell clonal expansion, MHC class II antigen presentation, zwitterionic polysaccharides, CDR3 loop, T cell receptor repertoire, immune homeostasis
- MeSH terms
- Animals, Bacteroides fragilis, Immunologic Memory, Lymphocyte Activation, Polysaccharides, Bacterial, CD4-Positive T-Lymphocytes, Bacterial Capsules, Receptors, Antigen, T-Cell, alpha-beta, Complementarity Determining Regions, Mice
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