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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45 Scopus citations

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 (US)
Article number12506
JournalNature communications
Volume7
DOIs
StatePublished - Aug 16 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Meermeier, E. W., Laugel, B. F., Sewell, A. K., Corbett, A. J., Rossjohn, J., McCluskey, J., Harriff, M. J., Franks, T., Gold, M. C., & Lewinsohn, D. M. (2016). Human TRAV1-2-negative MR1-restricted T cells detect S. pyogenes and alternatives to MAIT riboflavin-based antigens. Nature communications, 7, [12506]. https://doi.org/10.1038/ncomms12506