MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage

Autores
Gold, Marielle C.; McLaren, James E.; Reistetter, Joseph A.; Smyk Pearson, Sue; Ladell, Kristin; Swarbrick, Gwendolyn M.; Yu, Yik Y. L.; Hansen, Ted H.; Lund, Ole; Nielsen, Morten; Gerritsen, Bram; Kesmir, Can; Miles, John J.; Lewinsohn, Deborah A.; Price, David A.; Lewinsohn, David M.
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mucosal-associated invariant T (MAIT) cells express a semi-invariant T cell receptor (TCR) that detects microbial metabolites presented by the nonpolymorphic major histocompatibility complex (MHC)–like molecule MR1. The highly conserved nature of MR1 in conjunction with biased MAIT TCRα chain usage is widely thought to indicate limited ligand presentation and discrimination within a pattern-like recognition system. Here, we evaluated the TCR repertoire of MAIT cells responsive to three classes of microbes. Substantial diversity and heterogeneity were apparent across the functional MAIT cell repertoire as a whole, especially for TCRβ chain sequences. Moreover, different pathogen-specific responses were characterized by distinct TCR usage, both between and within individuals, suggesting that MAIT cell adaptation was a direct consequence of exposure to various exogenous MR1-restricted epitopes. In line with this interpretation, MAIT cell clones with distinct TCRs responded differentially to a riboflavin metabolite. These results suggest that MAIT cells can discriminate between pathogen-derived ligands in a clonotype-dependent manner, providing a basis for adaptive memory via recruitment of specific repertoires shaped by microbial exposure.
Fil: Gold, Marielle C.. Oregon Health & Science University; Estados Unidos
Fil: McLaren, James E.. Cardiff University; Reino Unido
Fil: Reistetter, Joseph A.. Oregon Health & Science University; Estados Unidos
Fil: Smyk Pearson, Sue. Oregon Health & Science University; Estados Unidos
Fil: Ladell, Kristin. Cardiff University; Reino Unido
Fil: Swarbrick, Gwendolyn M.. Oregon Health & Science University; Estados Unidos
Fil: Yu, Yik Y. L.. Washington University in St. Louis; Estados Unidos
Fil: Hansen, Ted H.. Washington University in St. Louis; Estados Unidos
Fil: Lund, Ole. Technical University of Denmark; Dinamarca
Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Gerritsen, Bram. Utrecht Univeristy; Países Bajos
Fil: Kesmir, Can. Utrecht Univeristy; Países Bajos
Fil: Miles, John J.. Cardiff University; Reino Unido
Fil: Lewinsohn, Deborah A.. Oregon Health & Science University; Estados Unidos
Fil: Price, David A.. Cardiff University; Reino Unido. National Institutes of Health; Estados Unidos
Fil: Lewinsohn, David M.. Oregon Health & Science University; Estados Unidos
Materia
MAIT
T cell
T cell receptor
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/18089
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/18089
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usageGold, Marielle C.McLaren, James E.Reistetter, Joseph A.Smyk Pearson, SueLadell, KristinSwarbrick, Gwendolyn M.Yu, Yik Y. L.Hansen, Ted H.Lund, OleNielsen, MortenGerritsen, BramKesmir, CanMiles, John J.Lewinsohn, Deborah A.Price, David A.Lewinsohn, David M.MAITT cellT cell receptorhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Mucosal-associated invariant T (MAIT) cells express a semi-invariant T cell receptor (TCR) that detects microbial metabolites presented by the nonpolymorphic major histocompatibility complex (MHC)–like molecule MR1. The highly conserved nature of MR1 in conjunction with biased MAIT TCRα chain usage is widely thought to indicate limited ligand presentation and discrimination within a pattern-like recognition system. Here, we evaluated the TCR repertoire of MAIT cells responsive to three classes of microbes. Substantial diversity and heterogeneity were apparent across the functional MAIT cell repertoire as a whole, especially for TCRβ chain sequences. Moreover, different pathogen-specific responses were characterized by distinct TCR usage, both between and within individuals, suggesting that MAIT cell adaptation was a direct consequence of exposure to various exogenous MR1-restricted epitopes. In line with this interpretation, MAIT cell clones with distinct TCRs responded differentially to a riboflavin metabolite. These results suggest that MAIT cells can discriminate between pathogen-derived ligands in a clonotype-dependent manner, providing a basis for adaptive memory via recruitment of specific repertoires shaped by microbial exposure.Fil: Gold, Marielle C.. Oregon Health & Science University; Estados UnidosFil: McLaren, James E.. Cardiff University; Reino UnidoFil: Reistetter, Joseph A.. Oregon Health & Science University; Estados UnidosFil: Smyk Pearson, Sue. Oregon Health & Science University; Estados UnidosFil: Ladell, Kristin. Cardiff University; Reino UnidoFil: Swarbrick, Gwendolyn M.. Oregon Health & Science University; Estados UnidosFil: Yu, Yik Y. L.. Washington University in St. Louis; Estados UnidosFil: Hansen, Ted H.. Washington University in St. Louis; Estados UnidosFil: Lund, Ole. Technical University of Denmark; DinamarcaFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Gerritsen, Bram. Utrecht Univeristy; Países BajosFil: Kesmir, Can. Utrecht Univeristy; Países BajosFil: Miles, John J.. Cardiff University; Reino UnidoFil: Lewinsohn, Deborah A.. Oregon Health & Science University; Estados UnidosFil: Price, David A.. Cardiff University; Reino Unido. National Institutes of Health; Estados UnidosFil: Lewinsohn, David M.. Oregon Health & Science University; Estados UnidosRockefeller Univ Press2014-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/18089Gold, Marielle C.; McLaren, James E.; Reistetter, Joseph A.; Smyk Pearson, Sue; Ladell, Kristin; et al.; MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage; Rockefeller Univ Press; Journal Of Experimental Medicine; 211; 8; 7-2014; 1601-16100022-1007CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://jem.rupress.org/content/211/8/1601.longinfo:eu-repo/semantics/altIdentifier/doi/10.1084/jem.20140507info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113934/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:00:31Zoai:ri.conicet.gov.ar:11336/18089instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:00:32.253CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage
title MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage
spellingShingle MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage
Gold, Marielle C.
MAIT
T cell
T cell receptor
title_short MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage
title_full MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage
title_fullStr MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage
title_full_unstemmed MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage
title_sort MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage
dc.creator.none.fl_str_mv Gold, Marielle C.
McLaren, James E.
Reistetter, Joseph A.
Smyk Pearson, Sue
Ladell, Kristin
Swarbrick, Gwendolyn M.
Yu, Yik Y. L.
Hansen, Ted H.
Lund, Ole
Nielsen, Morten
Gerritsen, Bram
Kesmir, Can
Miles, John J.
Lewinsohn, Deborah A.
Price, David A.
Lewinsohn, David M.
author Gold, Marielle C.
author_facet Gold, Marielle C.
McLaren, James E.
Reistetter, Joseph A.
Smyk Pearson, Sue
Ladell, Kristin
Swarbrick, Gwendolyn M.
Yu, Yik Y. L.
Hansen, Ted H.
Lund, Ole
Nielsen, Morten
Gerritsen, Bram
Kesmir, Can
Miles, John J.
Lewinsohn, Deborah A.
Price, David A.
Lewinsohn, David M.
author_role author
author2 McLaren, James E.
Reistetter, Joseph A.
Smyk Pearson, Sue
Ladell, Kristin
Swarbrick, Gwendolyn M.
Yu, Yik Y. L.
Hansen, Ted H.
Lund, Ole
Nielsen, Morten
Gerritsen, Bram
Kesmir, Can
Miles, John J.
Lewinsohn, Deborah A.
Price, David A.
Lewinsohn, David M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MAIT
T cell
T cell receptor
topic MAIT
T cell
T cell receptor
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Mucosal-associated invariant T (MAIT) cells express a semi-invariant T cell receptor (TCR) that detects microbial metabolites presented by the nonpolymorphic major histocompatibility complex (MHC)–like molecule MR1. The highly conserved nature of MR1 in conjunction with biased MAIT TCRα chain usage is widely thought to indicate limited ligand presentation and discrimination within a pattern-like recognition system. Here, we evaluated the TCR repertoire of MAIT cells responsive to three classes of microbes. Substantial diversity and heterogeneity were apparent across the functional MAIT cell repertoire as a whole, especially for TCRβ chain sequences. Moreover, different pathogen-specific responses were characterized by distinct TCR usage, both between and within individuals, suggesting that MAIT cell adaptation was a direct consequence of exposure to various exogenous MR1-restricted epitopes. In line with this interpretation, MAIT cell clones with distinct TCRs responded differentially to a riboflavin metabolite. These results suggest that MAIT cells can discriminate between pathogen-derived ligands in a clonotype-dependent manner, providing a basis for adaptive memory via recruitment of specific repertoires shaped by microbial exposure.
Fil: Gold, Marielle C.. Oregon Health & Science University; Estados Unidos
Fil: McLaren, James E.. Cardiff University; Reino Unido
Fil: Reistetter, Joseph A.. Oregon Health & Science University; Estados Unidos
Fil: Smyk Pearson, Sue. Oregon Health & Science University; Estados Unidos
Fil: Ladell, Kristin. Cardiff University; Reino Unido
Fil: Swarbrick, Gwendolyn M.. Oregon Health & Science University; Estados Unidos
Fil: Yu, Yik Y. L.. Washington University in St. Louis; Estados Unidos
Fil: Hansen, Ted H.. Washington University in St. Louis; Estados Unidos
Fil: Lund, Ole. Technical University of Denmark; Dinamarca
Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina
Fil: Gerritsen, Bram. Utrecht Univeristy; Países Bajos
Fil: Kesmir, Can. Utrecht Univeristy; Países Bajos
Fil: Miles, John J.. Cardiff University; Reino Unido
Fil: Lewinsohn, Deborah A.. Oregon Health & Science University; Estados Unidos
Fil: Price, David A.. Cardiff University; Reino Unido. National Institutes of Health; Estados Unidos
Fil: Lewinsohn, David M.. Oregon Health & Science University; Estados Unidos
description Mucosal-associated invariant T (MAIT) cells express a semi-invariant T cell receptor (TCR) that detects microbial metabolites presented by the nonpolymorphic major histocompatibility complex (MHC)–like molecule MR1. The highly conserved nature of MR1 in conjunction with biased MAIT TCRα chain usage is widely thought to indicate limited ligand presentation and discrimination within a pattern-like recognition system. Here, we evaluated the TCR repertoire of MAIT cells responsive to three classes of microbes. Substantial diversity and heterogeneity were apparent across the functional MAIT cell repertoire as a whole, especially for TCRβ chain sequences. Moreover, different pathogen-specific responses were characterized by distinct TCR usage, both between and within individuals, suggesting that MAIT cell adaptation was a direct consequence of exposure to various exogenous MR1-restricted epitopes. In line with this interpretation, MAIT cell clones with distinct TCRs responded differentially to a riboflavin metabolite. These results suggest that MAIT cells can discriminate between pathogen-derived ligands in a clonotype-dependent manner, providing a basis for adaptive memory via recruitment of specific repertoires shaped by microbial exposure.
publishDate 2014
dc.date.none.fl_str_mv 2014-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/18089
Gold, Marielle C.; McLaren, James E.; Reistetter, Joseph A.; Smyk Pearson, Sue; Ladell, Kristin; et al.; MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage; Rockefeller Univ Press; Journal Of Experimental Medicine; 211; 8; 7-2014; 1601-1610
0022-1007
CONICET Digital
CONICET
url http://hdl.handle.net/11336/18089
identifier_str_mv Gold, Marielle C.; McLaren, James E.; Reistetter, Joseph A.; Smyk Pearson, Sue; Ladell, Kristin; et al.; MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage; Rockefeller Univ Press; Journal Of Experimental Medicine; 211; 8; 7-2014; 1601-1610
0022-1007
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://jem.rupress.org/content/211/8/1601.long
info:eu-repo/semantics/altIdentifier/doi/10.1084/jem.20140507
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113934/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Rockefeller Univ Press
publisher.none.fl_str_mv Rockefeller Univ Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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