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

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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113934/
https://www.ncbi.nlm.nih.gov/pubmed/25049333
http://dx.doi.org/10.1084/jem.20140507
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author 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_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_sort Gold, Marielle C.
collection PubMed
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.
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spelling pubmed-41139342015-01-28 MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage 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. J Exp Med Article 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. The Rockefeller University Press 2014-07-28 /pmc/articles/PMC4113934/ /pubmed/25049333 http://dx.doi.org/10.1084/jem.20140507 Text en © 2014 Gold et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
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.
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
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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4113934/
https://www.ncbi.nlm.nih.gov/pubmed/25049333
http://dx.doi.org/10.1084/jem.20140507
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