Non-canonicaly recruited TCRαβCD8αα IELs recognize microbial antigens

Abstract In the gut, various subsets of intraepithelial T cells (IELs) respond to self or non-self-antigens derived from the body, diet, commensal and pathogenic microbiota. Dominant subset of IELs in the small intestine are TCRαβCD8αα+ cells, which are derived from immature thymocytes that express...

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Autores principales:	Lukasz Wojciech, Edyta Szurek, Michal Kuczma, Anna Cebula, Wessam R. Elhefnawy, Maciej Pietrzak, Grzegorz Rempala, Leszek Ignatowicz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/17fae1688ad846f5801bedc8c82b0475
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spelling	oai:doaj.org-article:17fae1688ad846f5801bedc8c82b04752021-12-02T15:07:46ZNon-canonicaly recruited TCRαβCD8αα IELs recognize microbial antigens10.1038/s41598-018-29073-72045-2322https://doaj.org/article/17fae1688ad846f5801bedc8c82b04752018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29073-7https://doaj.org/toc/2045-2322Abstract In the gut, various subsets of intraepithelial T cells (IELs) respond to self or non-self-antigens derived from the body, diet, commensal and pathogenic microbiota. Dominant subset of IELs in the small intestine are TCRαβCD8αα+ cells, which are derived from immature thymocytes that express self-reactive TCRs. Although most of TCRαβCD8αα+ IELs are thymus-derived, their repertoire adapts to microbial flora. Here, using high throughput TCR sequencing we examined how clonal diversity of TCRαβCD8αα+ IELs changes upon exposure to commensal-derived antigens. We found that fraction of CD8αα+ IELs and CD4+ T cells express identical αβTCRs and this overlap raised parallel to a surge in the diversity of microbial flora. We also found that an opportunistic pathogen (Staphylococcus aureus) isolated from mouse small intestine specifically activated CD8αα+ IELs and CD4+ derived T cell hybridomas suggesting that some of TCRαβCD8αα+ clones with microbial specificities have extrathymic origin. We also report that CD8ααCD4+ IELs and Foxp3CD4+ T cells from the small intestine shared many αβTCRs, regardless whether the later subset was isolated from Foxp3CNS1 sufficient or Foxp3CNS1 deficient mice that lacks peripherally-derived Tregs. Overall, our results imply that repertoire of TCRαβCD8αα+ in small intestine expends in situ in response to changes in microbial flora.Lukasz WojciechEdyta SzurekMichal KuczmaAnna CebulaWessam R. ElhefnawyMaciej PietrzakGrzegorz RempalaLeszek IgnatowiczNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lukasz Wojciech Edyta Szurek Michal Kuczma Anna Cebula Wessam R. Elhefnawy Maciej Pietrzak Grzegorz Rempala Leszek Ignatowicz Non-canonicaly recruited TCRαβCD8αα IELs recognize microbial antigens
description	Abstract In the gut, various subsets of intraepithelial T cells (IELs) respond to self or non-self-antigens derived from the body, diet, commensal and pathogenic microbiota. Dominant subset of IELs in the small intestine are TCRαβCD8αα+ cells, which are derived from immature thymocytes that express self-reactive TCRs. Although most of TCRαβCD8αα+ IELs are thymus-derived, their repertoire adapts to microbial flora. Here, using high throughput TCR sequencing we examined how clonal diversity of TCRαβCD8αα+ IELs changes upon exposure to commensal-derived antigens. We found that fraction of CD8αα+ IELs and CD4+ T cells express identical αβTCRs and this overlap raised parallel to a surge in the diversity of microbial flora. We also found that an opportunistic pathogen (Staphylococcus aureus) isolated from mouse small intestine specifically activated CD8αα+ IELs and CD4+ derived T cell hybridomas suggesting that some of TCRαβCD8αα+ clones with microbial specificities have extrathymic origin. We also report that CD8ααCD4+ IELs and Foxp3CD4+ T cells from the small intestine shared many αβTCRs, regardless whether the later subset was isolated from Foxp3CNS1 sufficient or Foxp3CNS1 deficient mice that lacks peripherally-derived Tregs. Overall, our results imply that repertoire of TCRαβCD8αα+ in small intestine expends in situ in response to changes in microbial flora.
format	article
author	Lukasz Wojciech Edyta Szurek Michal Kuczma Anna Cebula Wessam R. Elhefnawy Maciej Pietrzak Grzegorz Rempala Leszek Ignatowicz
author_facet	Lukasz Wojciech Edyta Szurek Michal Kuczma Anna Cebula Wessam R. Elhefnawy Maciej Pietrzak Grzegorz Rempala Leszek Ignatowicz
author_sort	Lukasz Wojciech
title	Non-canonicaly recruited TCRαβCD8αα IELs recognize microbial antigens
title_short	Non-canonicaly recruited TCRαβCD8αα IELs recognize microbial antigens
title_full	Non-canonicaly recruited TCRαβCD8αα IELs recognize microbial antigens
title_fullStr	Non-canonicaly recruited TCRαβCD8αα IELs recognize microbial antigens
title_full_unstemmed	Non-canonicaly recruited TCRαβCD8αα IELs recognize microbial antigens
title_sort	non-canonicaly recruited tcrαβcd8αα iels recognize microbial antigens
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/17fae1688ad846f5801bedc8c82b0475
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Non-canonicaly recruited TCRαβCD8αα IELs recognize microbial antigens

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