2. Academic Validation
  3. MR1 displays the microbial metabolome driving selective MR1-restricted T cell receptor usage

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

  • Sci Immunol. 2018 Jul 13;3(25):eaao2556. doi: 10.1126/sciimmunol.aao2556.
Melanie J Harriff 1 2,  Curtis McMurtrey 3,  Cara A Froyd 4,  Haihong Jin 5,  Meghan Cansler 6,  Megan Null 6,  Aneta Worley 1,  Erin W Meermeier 2,  Gwendolyn Swarbrick 6,  Aaron Nilsen 1 5 7,  Deborah A Lewinsohn 6,  William Hildebrand 8,  Erin J Adams 9,  David M Lewinsohn 10 2
Affiliations

Affiliations

  • 1 VA Portland Health Care System, Research and Development, 3710 Southwest U.S. Veterans Hospital Road, Portland, OR 97239, USA.
  • 2 Department of Pulmonary and Critical Care Medicine, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA.
  • 3 Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
  • 4 Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
  • 5 Oregon Health & Science University Medicinal Chemistry Core, Portland, OR 97239, USA.
  • 6 Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239, USA.
  • 7 Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239, USA.
  • 8 Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. [email protected].
  • 9 Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA. [email protected].
  • 10 VA Portland Health Care System, Research and Development, 3710 Southwest U.S. Veterans Hospital Road, Portland, OR 97239, USA. [email protected].
PMID: 30006464 DOI: 10.1126/sciimmunol.aao2556
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.

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