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 Harriff, Tamera Franks, Marielle Gold, David Lewinsohn

Research output: Contribution to journalArticle

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

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riboflavin
T-cells
Riboflavin
antigens
Clone Cells
T-Lymphocytes
Antigens
metabolites
infectious diseases
Metabolites
Streptococcus pyogenes
Viral Tumor Antigens
T-Lymphocyte Subsets
Mycobacterium
HLA Antigens
streptococcus
Infection
staining
microorganisms
axioms

ASJC Scopus subject areas

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

Cite this

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; Franks, Tamera; Gold, Marielle; Lewinsohn, David.

In: Nature Communications, Vol. 7, 12506, 16.08.2016.

Research output: Contribution to journalArticle

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