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Human TRAV1-2-negative MR1-restricted T cells detect S. pyogenes and alternatives to MAIT riboflavin-based antigens

Meermeier, Erin W., Laugel, Bruno F., Sewell, Andrew K., Corbett, Alexandra J., Rossjohn, Jamie, McCluskey, James, Harriff, Melanie J., Franks, Tamera, Gold, Marielle C. and Lewinsohn, David M. 2016. Human TRAV1-2-negative MR1-restricted T cells detect S. pyogenes and alternatives to MAIT riboflavin-based antigens. Nature Communications 7 , 12506. 10.1038/ncomms12506

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Abstract

Mucosal-associated invariant T (MAIT) cells are thought to detect microbial antigens presented by the HLA-Ib molecule MR1 through the exclusive use of a TRAV1-2-containing TCRα. Here we use MR1 tetramer staining and ex vivo analysis with mycobacteria-infected MR1-deficient cells to demonstrate the presence of functional human MR1-restricted T cells that lack TRAV1-2. We characterize an MR1-restricted clone that expresses the TRAV12-2 TCRα, which lacks residues previously shown to be critical for MR1-antigen recognition. In contrast to TRAV1-2+ MAIT cells, this TRAV12-2-expressing clone displays a distinct pattern of microbial recognition by detecting infection with the riboflavin auxotroph Streptococcus pyogenes. As known MAIT antigens are derived from riboflavin metabolites, this suggests that TRAV12-2+ clone recognizes unique antigens. Thus, MR1-restricted T cells can discriminate between microbes in a TCR-dependent manner. We postulate that additional MR1-restricted T-cell subsets may play a unique role in defence against infection by broadening the recognition of microbial metabolites.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Antimicrobial responses; Bacterial host response; T-cell receptor
Additional Information: This work is licensed under a Creative Commons Attribution 4.0 International License.
Publisher: Nature Publishing Group
ISSN: 2041-1723
Date of First Compliant Deposit: 24 May 2017
Date of Acceptance: 7 July 2016
Last Modified: 11 Jul 2019 12:18
URI: http://orca-mwe.cf.ac.uk/id/eprint/100737

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