MR1 displays the microbial metabolome driving selective MR1-restricted T cell receptor usage.
Melanie J HarriffCurtis McMurtreyCara A FroydHaihong JinMeghan CanslerMegan NullAneta WorleyErin W MeermeierGwendolyn SwarbrickAaron NilsenDeborah A LewinsohnWilliam HildebrandErin J AdamsDavid M LewinsohnPublished in: Science immunology (2019)
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.
Keyphrases
- contrast enhanced
- escherichia coli
- mycobacterium tuberculosis
- magnetic resonance
- mass spectrometry
- magnetic resonance imaging
- high resolution
- oxidative stress
- gram negative
- multidrug resistant
- electronic health record
- gene expression
- signaling pathway
- deep learning
- pseudomonas aeruginosa
- antimicrobial resistance
- big data
- artificial intelligence
- pulmonary tuberculosis
- tandem mass spectrometry