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

Standard

The CD4+ T cell response to a commensal-derived epitope transitions from a tolerant to an inflammatory state in Crohn's disease. / Pedersen, Thomas K.; Brown, Eric M.; Plichta, Damian R.; Johansen, Joachim; Twardus, Shaina W.; Delorey, Toni M.; Lau, Helena; Vlamakis, Hera; Moon, James J.; Xavier, Ramnik J.; Graham, Daniel B.

In: Immunity, Vol. 55, No. 10, 2022, p. 1909-1923.e6.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Pedersen, TK, Brown, EM, Plichta, DR, Johansen, J, Twardus, SW, Delorey, TM, Lau, H, Vlamakis, H, Moon, JJ, Xavier, RJ & Graham, DB 2022, 'The CD4+ T cell response to a commensal-derived epitope transitions from a tolerant to an inflammatory state in Crohn's disease', Immunity, vol. 55, no. 10, pp. 1909-1923.e6. https://doi.org/10.1016/j.immuni.2022.08.016

APA

Pedersen, T. K., Brown, E. M., Plichta, D. R., Johansen, J., Twardus, S. W., Delorey, T. M., Lau, H., Vlamakis, H., Moon, J. J., Xavier, R. J., & Graham, D. B. (2022). The CD4+ T cell response to a commensal-derived epitope transitions from a tolerant to an inflammatory state in Crohn's disease. Immunity, 55(10), 1909-1923.e6. https://doi.org/10.1016/j.immuni.2022.08.016

Vancouver

Pedersen TK, Brown EM, Plichta DR, Johansen J, Twardus SW, Delorey TM et al. The CD4+ T cell response to a commensal-derived epitope transitions from a tolerant to an inflammatory state in Crohn's disease. Immunity. 2022;55(10):1909-1923.e6. https://doi.org/10.1016/j.immuni.2022.08.016

Author

Pedersen, Thomas K. ; Brown, Eric M. ; Plichta, Damian R. ; Johansen, Joachim ; Twardus, Shaina W. ; Delorey, Toni M. ; Lau, Helena ; Vlamakis, Hera ; Moon, James J. ; Xavier, Ramnik J. ; Graham, Daniel B. / The CD4+ T cell response to a commensal-derived epitope transitions from a tolerant to an inflammatory state in Crohn's disease. In: Immunity. 2022 ; Vol. 55, No. 10. pp. 1909-1923.e6.

Bibtex

@article{2f44a8f3c64349709de0680d137bf085,
title = "The CD4+ T cell response to a commensal-derived epitope transitions from a tolerant to an inflammatory state in Crohn's disease",
abstract = "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.",
keywords = "epitope prediction, immunodominance, inflammation, inflammatory bowel disease, metagenomics, MHC class II, microbial antigens, microbiome, mucosal immunology, T cells",
author = "Pedersen, {Thomas K.} and Brown, {Eric M.} and Plichta, {Damian R.} and Joachim Johansen and Twardus, {Shaina W.} and Delorey, {Toni M.} and Helena Lau and Hera Vlamakis and Moon, {James J.} and Xavier, {Ramnik J.} and Graham, {Daniel B.}",
note = "Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
doi = "10.1016/j.immuni.2022.08.016",
language = "English",
volume = "55",
pages = "1909--1923.e6",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "10",

}

RIS

TY - JOUR

T1 - The CD4+ T cell response to a commensal-derived epitope transitions from a tolerant to an inflammatory state in Crohn's disease

AU - Pedersen, Thomas K.

AU - Brown, Eric M.

AU - Plichta, Damian R.

AU - Johansen, Joachim

AU - Twardus, Shaina W.

AU - Delorey, Toni M.

AU - Lau, Helena

AU - Vlamakis, Hera

AU - Moon, James J.

AU - Xavier, Ramnik J.

AU - Graham, Daniel B.

N1 - Publisher Copyright: © 2022 Elsevier Inc.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - epitope prediction

KW - immunodominance

KW - inflammation

KW - inflammatory bowel disease

KW - metagenomics

KW - MHC class II

KW - microbial antigens

KW - microbiome

KW - mucosal immunology

KW - T cells

U2 - 10.1016/j.immuni.2022.08.016

DO - 10.1016/j.immuni.2022.08.016

M3 - Journal article

C2 - 36115338

AN - SCOPUS:85139305057

VL - 55

SP - 1909-1923.e6

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 10

ER -

ID: 323190917