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. ORCID: https://orcid.org/0000-0003-3194-3135, 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

Preview

PDF - Published Version Available under License Creative Commons Attribution Non-commercial. Download (1MB) | Preview

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:	03 May 2023 13:06
URI:	https://orca.cardiff.ac.uk/id/eprint/100737

Citation Data

Cited 77 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item