Commensal bacteria maintain a Qa-1b-restricted unconventional CD8+ T population in gut epithelium

Intestinal intraepithelial lymphocytes (IELs) are characterized by an unusual phenotype and developmental pathway, yet their specific ligands and functions remain largely unknown. Here by analysis of QFL T cells, a population of CD8+ T cells critical for monitoring the MHC I antigen processing pathw...

Full description

Bibliographic Details
Main Authors: Jian Guan, J David Peske, Michael Manoharan Valerio, Chansu Park, Ellen A Robey, Scheherazade Sadegh-Nasseri
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2023-12-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/90466
_version_ 1797383202384379904
author Jian Guan
J David Peske
Michael Manoharan Valerio
Chansu Park
Ellen A Robey
Scheherazade Sadegh-Nasseri
author_facet Jian Guan
J David Peske
Michael Manoharan Valerio
Chansu Park
Ellen A Robey
Scheherazade Sadegh-Nasseri
author_sort Jian Guan
collection DOAJ
description Intestinal intraepithelial lymphocytes (IELs) are characterized by an unusual phenotype and developmental pathway, yet their specific ligands and functions remain largely unknown. Here by analysis of QFL T cells, a population of CD8+ T cells critical for monitoring the MHC I antigen processing pathway, we established that unconventional Qa-1b-restricted CD8+ T cells are abundant in intestinal epithelium. We found that QFL T cells showed a Qa-1b-dependent unconventional phenotype in the spleen and small intestine of naïve wild-type mice. The splenic QFL T cells showed innate-like functionality exemplified by rapid response to cytokines or antigens, while the gut population was refractory to stimuli. Microbiota was required for the maintenance, but not the initial gut homing of QFL T cells. Moreover, monocolonization with Pediococcus pentosaceus, which expresses a peptide that cross-activated QFL T cells, was sufficient to maintain QFL T cells in the intestine. Thus, microbiota is critical for shaping the Qa-1b-restricted IEL landscape.
first_indexed 2024-03-08T21:17:13Z
format Article
id doaj.art-54430899bea94fd7b55a65b2c274a757
institution Directory Open Access Journal
issn 2050-084X
language English
last_indexed 2024-03-08T21:17:13Z
publishDate 2023-12-01
publisher eLife Sciences Publications Ltd
record_format Article
series eLife
spelling doaj.art-54430899bea94fd7b55a65b2c274a7572023-12-21T15:01:50ZengeLife Sciences Publications LtdeLife2050-084X2023-12-011210.7554/eLife.90466Commensal bacteria maintain a Qa-1b-restricted unconventional CD8+ T population in gut epitheliumJian Guan0https://orcid.org/0000-0002-0118-6578J David Peske1Michael Manoharan Valerio2Chansu Park3Ellen A Robey4https://orcid.org/0000-0002-3630-5266Scheherazade Sadegh-Nasseri5https://orcid.org/0000-0002-8127-1720Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States; Institute of Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States; Institute of Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, United StatesDivision of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, United States; Institute of Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, United StatesDivision of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, United StatesIntestinal intraepithelial lymphocytes (IELs) are characterized by an unusual phenotype and developmental pathway, yet their specific ligands and functions remain largely unknown. Here by analysis of QFL T cells, a population of CD8+ T cells critical for monitoring the MHC I antigen processing pathway, we established that unconventional Qa-1b-restricted CD8+ T cells are abundant in intestinal epithelium. We found that QFL T cells showed a Qa-1b-dependent unconventional phenotype in the spleen and small intestine of naïve wild-type mice. The splenic QFL T cells showed innate-like functionality exemplified by rapid response to cytokines or antigens, while the gut population was refractory to stimuli. Microbiota was required for the maintenance, but not the initial gut homing of QFL T cells. Moreover, monocolonization with Pediococcus pentosaceus, which expresses a peptide that cross-activated QFL T cells, was sufficient to maintain QFL T cells in the intestine. Thus, microbiota is critical for shaping the Qa-1b-restricted IEL landscape.https://elifesciences.org/articles/90466IELunconventional TmicrobiotaMHC-E
spellingShingle Jian Guan
J David Peske
Michael Manoharan Valerio
Chansu Park
Ellen A Robey
Scheherazade Sadegh-Nasseri
Commensal bacteria maintain a Qa-1b-restricted unconventional CD8+ T population in gut epithelium
eLife
IEL
unconventional T
microbiota
MHC-E
title Commensal bacteria maintain a Qa-1b-restricted unconventional CD8+ T population in gut epithelium
title_full Commensal bacteria maintain a Qa-1b-restricted unconventional CD8+ T population in gut epithelium
title_fullStr Commensal bacteria maintain a Qa-1b-restricted unconventional CD8+ T population in gut epithelium
title_full_unstemmed Commensal bacteria maintain a Qa-1b-restricted unconventional CD8+ T population in gut epithelium
title_short Commensal bacteria maintain a Qa-1b-restricted unconventional CD8+ T population in gut epithelium
title_sort commensal bacteria maintain a qa 1b restricted unconventional cd8 t population in gut epithelium
topic IEL
unconventional T
microbiota
MHC-E
url https://elifesciences.org/articles/90466
work_keys_str_mv AT jianguan commensalbacteriamaintainaqa1brestrictedunconventionalcd8tpopulationingutepithelium
AT jdavidpeske commensalbacteriamaintainaqa1brestrictedunconventionalcd8tpopulationingutepithelium
AT michaelmanoharanvalerio commensalbacteriamaintainaqa1brestrictedunconventionalcd8tpopulationingutepithelium
AT chansupark commensalbacteriamaintainaqa1brestrictedunconventionalcd8tpopulationingutepithelium
AT ellenarobey commensalbacteriamaintainaqa1brestrictedunconventionalcd8tpopulationingutepithelium
AT scheherazadesadeghnasseri commensalbacteriamaintainaqa1brestrictedunconventionalcd8tpopulationingutepithelium