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., and Lewinsohn, David M. (2014) MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage. The Journal of Experimental Medicine, 211 (8). pp. 1601-1610.

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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 ID: 45057
Item Type: Article (Research - C1)
ISSN: 1540-9538
Additional Information:

© 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/).

Funders: Department of Veterans Affairs (DVA), Portland VA Medical Center (PVAMC), National Institutes of Health (NIH), Muscular Immunology Studies Team (MIST), National Institute of Allergy and Infectious Diseases (NIAID), Wellcome Trust (WT)
Projects and Grants: MIST U01 AI095776-01, NIH grant AI046553
Date Deposited: 09 Aug 2016 05:46
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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