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

Gold, Marielle C., McLaren, James E. ORCID: https://orcid.org/0000-0002-7021-5934, Reistetter, Jospeh A., Smyk-Pearson, Sue, Ladell, Kristin ORCID: https://orcid.org/0000-0002-9856-2938, 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. ORCID: https://orcid.org/0000-0001-9416-2737 and Lewinsohn, David M. 2014. MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage. Journal of Experimental Medicine 211 (8) , pp. 1601-1610. 10.1084/jem.20140507

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Additional Information:	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/).
Publisher:	Rockefeller University Press
ISSN:	0022-1007
Date of First Compliant Deposit:	6 September 2017
Date of Acceptance:	18 June 2014
Last Modified:	10 Jun 2023 17:06
URI:	https://orca.cardiff.ac.uk/id/eprint/85485

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