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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2014
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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. |
format | Online Article Text |
id | pubmed-4113934 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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