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

Erin W. Meermeier, Bruno F. Laugel, Andrew K. Sewell, Alexandra J. Corbett, Jamie Rossjohn, James McCluskey, Melanie J. Harriff, Tamera Franks, Marielle C. Gold, David M. Lewinsohn

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67 Citations (Scopus)

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.

Original languageEnglish
Article number12506
Number of pages12
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 16 Aug 2016

Keywords

  • antimicrobial responses
  • bacterial host response
  • T-cell receptor

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