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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.
Afiliación
  • Pedersen TK; Infectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Disease Systems Immunology, Department of Biotechnology and Biomedicine, Section for Protein Science and Biotherapeutics, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
  • Brown EM; Infectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Plichta DR; Infectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Johansen J; Infectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
  • Twardus SW; Center for the Study of Inflammatory Bowel Disease, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Delorey TM; Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Lau H; Center for the Study of Inflammatory Bowel Disease, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Vlamakis H; Infectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Moon JJ; Center for Immunology and Inflammatory Diseases and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
  • Xavier RJ; Infectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Center for the Study of Infla
  • Graham DB; Infectious Disease and Microbiome Program, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Center for the Study of Infla
Immunity ; 55(10): 1909-1923.e6, 2022 10 11.
Article en En | MEDLINE | ID: mdl-36115338
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.
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Texto completo: 1 Colección: 01-internacional Asunto principal: Enfermedad de Crohn / Epítopos Inmunodominantes Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Dinamarca
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Asunto principal: Enfermedad de Crohn / Epítopos Inmunodominantes Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Dinamarca