The CD4+ T cell response to a commensal-derived epitope transitions from a tolerant to an inflammatory state in Crohn's disease
Research output: Contribution to journal › Journal article › Research › peer-review
Reciprocal interactions between host T helper cells and gut microbiota enforce local immunological tolerance and modulate extra-intestinal immunity. However, our understanding of antigen-specific tolerance to the microbiome is limited. Here, we developed a systematic approach to predict HLA class-II-specific epitopes using the humanized bacteria-originated T cell antigen (hBOTA) algorithm. We identified a diverse set of microbiome epitopes spanning all major taxa that are compatible with presentation by multiple HLA-II alleles. In particular, we uncovered an immunodominant epitope from the TonB-dependent receptor SusC that was universally recognized and ubiquitous among Bacteroidales. In healthy human subjects, SusC-reactive T cell responses were characterized by IL-10-dominant cytokine profiles, whereas in patients with active Crohn's disease, responses were associated with elevated IL-17A. Our results highlight the potential of targeted antigen discovery within the microbiome to reveal principles of tolerance and functional transitions during inflammation.
Original language | English |
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Journal | Immunity |
Volume | 55 |
Issue number | 10 |
Pages (from-to) | 1909-1923.e6 |
ISSN | 1074-7613 |
DOIs | |
Publication status | Published - 2022 |
Bibliographical note
Publisher Copyright:
© 2022 Elsevier Inc.
- epitope prediction, immunodominance, inflammation, inflammatory bowel disease, metagenomics, MHC class II, microbial antigens, microbiome, mucosal immunology, T cells
Research areas
Links
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9890645/pdf/nihms-1865190.pdf
Accepted author manuscript
ID: 323190917