MR1 displays the microbial metabolome driving selective MR1-restricted T cell receptor usage

Melanie Harriff, Curtis McMurtrey, Cara A. Froyd, Haihong Jin, Meghan Cansler, Megan Null, Aneta Worley, Erin W. Meermeier, Gwendolyn Swarbrick, Aaron Nilsen, Deborah Lewinsohn, William Hildebrand, Erin J. Adams, David Lewinsohn

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Abstract

MR1-restricted T cells (MR1Ts) are a T cell subset that recognize and mediate host defense to a broad array of microbial pathogens, including respiratory pathogens (e.g., Mycobacterium tuberculosis, Streptococcus pyogenes, and Francisella tularensis) and enteric pathogens (e.g., Escherichia coli and Salmonella species). Mucosal-associated invariant T (MAIT) cells, a subset of MR1Ts, were historically defined by the use of a semi-invariant T cell receptor (TCR) and recognition of small molecules derived from the riboflavin biosynthesis pathway presented on MR1. We used mass spectrometry to identify the repertoire of ligands presented by MR1 from the microbes E. coli and Mycobacterium smegmatis We found that the MR1 ligandome is unexpectedly broad, revealing functionally distinct ligands derived from E. coli and M. smegmatis The identification, synthesis, and functional analysis of mycobacterial ligands reveal that MR1T ligands can be distinguished by MR1Ts with diverse TCR usage. These data demonstrate that MR1 can serve as an immune sensor of the microbial ligandome.

Original languageEnglish (US)
JournalScience immunology
Volume3
Issue number25
DOIs
StatePublished - Jul 13 2018

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Harriff, M., McMurtrey, C., Froyd, C. A., Jin, H., Cansler, M., Null, M., Worley, A., Meermeier, E. W., Swarbrick, G., Nilsen, A., Lewinsohn, D., Hildebrand, W., Adams, E. J., & Lewinsohn, D. (2018). MR1 displays the microbial metabolome driving selective MR1-restricted T cell receptor usage. Science immunology, 3(25). https://doi.org/10.1126/sciimmunol.aao2556