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Tuning of human MAIT cell activation by commensal bacteria species and MR1 dependent T cell presentation

Human mucosal-associated invariant T (MAIT) cell receptors (TCRs) recognize bacterial riboflavin pathway metabolites through the MHC class 1-related molecule MR1. However, it is unclear whether MAIT cells discriminate between many species of the human microbiota. To address this, we developed an in...

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Autores principales: Tastan, Cihan, Karhan, Ece, Zhou, Wei, Fleming, Elizabeth, Voigt, Anita Y., Yao, Xudong, Wang, Lei, Horne, Meghan, Placek, Lindsey, Kozhaya, Lina, Oh, Julia, Unutmaz, Derya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279574/
https://www.ncbi.nlm.nih.gov/pubmed/30115998
http://dx.doi.org/10.1038/s41385-018-0072-x
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author Tastan, Cihan
Karhan, Ece
Zhou, Wei
Fleming, Elizabeth
Voigt, Anita Y.
Yao, Xudong
Wang, Lei
Horne, Meghan
Placek, Lindsey
Kozhaya, Lina
Oh, Julia
Unutmaz, Derya
author_facet Tastan, Cihan
Karhan, Ece
Zhou, Wei
Fleming, Elizabeth
Voigt, Anita Y.
Yao, Xudong
Wang, Lei
Horne, Meghan
Placek, Lindsey
Kozhaya, Lina
Oh, Julia
Unutmaz, Derya
author_sort Tastan, Cihan
collection PubMed
description Human mucosal-associated invariant T (MAIT) cell receptors (TCRs) recognize bacterial riboflavin pathway metabolites through the MHC class 1-related molecule MR1. However, it is unclear whether MAIT cells discriminate between many species of the human microbiota. To address this, we developed an in vitro functional assay through human T cells engineered for MAIT-TCRs (eMAIT-TCRs) stimulated by MR1-expressing antigen presenting cells (APC). We then screened 47 microbiota-associated bacterial species from different phyla for their eMAIT- TCR stimulatory capacities. Only bacteria species that encoded the riboflavin pathway were stimulatory for MAIT-TCRs. Most species that were high-stimulators belonged to Bacteroidetes and Proteobacteria phyla, whereas low/non-stimulator species were primarily Actinobacteria or Firmicutes. Activation of MAIT cells by high- vs low-stimulating bacteria also correlated with the level of riboflavin they secreted or after bacterial infection of macrophages. Remarkably, we found that human T cell subsets can also present riboflavin metabolites to MAIT cells in MR1- restricted fashion. This T-T cell mediated signaling also induced IFN𝛄, TNF and GranzymeB from MAIT cells, albeit at lower level than professional APC. These findings suggest that MAIT cells can discriminate and categorize complex human microbiota through computation of TCR signals depending on antigen load and presenting cells, and fine-tune their functional responses.
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spelling pubmed-62795742019-02-16 Tuning of human MAIT cell activation by commensal bacteria species and MR1 dependent T cell presentation Tastan, Cihan Karhan, Ece Zhou, Wei Fleming, Elizabeth Voigt, Anita Y. Yao, Xudong Wang, Lei Horne, Meghan Placek, Lindsey Kozhaya, Lina Oh, Julia Unutmaz, Derya Mucosal Immunol Article Human mucosal-associated invariant T (MAIT) cell receptors (TCRs) recognize bacterial riboflavin pathway metabolites through the MHC class 1-related molecule MR1. However, it is unclear whether MAIT cells discriminate between many species of the human microbiota. To address this, we developed an in vitro functional assay through human T cells engineered for MAIT-TCRs (eMAIT-TCRs) stimulated by MR1-expressing antigen presenting cells (APC). We then screened 47 microbiota-associated bacterial species from different phyla for their eMAIT- TCR stimulatory capacities. Only bacteria species that encoded the riboflavin pathway were stimulatory for MAIT-TCRs. Most species that were high-stimulators belonged to Bacteroidetes and Proteobacteria phyla, whereas low/non-stimulator species were primarily Actinobacteria or Firmicutes. Activation of MAIT cells by high- vs low-stimulating bacteria also correlated with the level of riboflavin they secreted or after bacterial infection of macrophages. Remarkably, we found that human T cell subsets can also present riboflavin metabolites to MAIT cells in MR1- restricted fashion. This T-T cell mediated signaling also induced IFN𝛄, TNF and GranzymeB from MAIT cells, albeit at lower level than professional APC. These findings suggest that MAIT cells can discriminate and categorize complex human microbiota through computation of TCR signals depending on antigen load and presenting cells, and fine-tune their functional responses. 2018-08-16 2018-11 /pmc/articles/PMC6279574/ /pubmed/30115998 http://dx.doi.org/10.1038/s41385-018-0072-x Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Tastan, Cihan
Karhan, Ece
Zhou, Wei
Fleming, Elizabeth
Voigt, Anita Y.
Yao, Xudong
Wang, Lei
Horne, Meghan
Placek, Lindsey
Kozhaya, Lina
Oh, Julia
Unutmaz, Derya
Tuning of human MAIT cell activation by commensal bacteria species and MR1 dependent T cell presentation
title Tuning of human MAIT cell activation by commensal bacteria species and MR1 dependent T cell presentation
title_full Tuning of human MAIT cell activation by commensal bacteria species and MR1 dependent T cell presentation
title_fullStr Tuning of human MAIT cell activation by commensal bacteria species and MR1 dependent T cell presentation
title_full_unstemmed Tuning of human MAIT cell activation by commensal bacteria species and MR1 dependent T cell presentation
title_short Tuning of human MAIT cell activation by commensal bacteria species and MR1 dependent T cell presentation
title_sort tuning of human mait cell activation by commensal bacteria species and mr1 dependent t cell presentation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279574/
https://www.ncbi.nlm.nih.gov/pubmed/30115998
http://dx.doi.org/10.1038/s41385-018-0072-x
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