Journal ArticleDOI
T-cell activation by transitory neo-antigens derived from distinct microbial pathways
Alexandra J. Corbett,Sidonia B G Eckle,Richard W Birkinshaw,Ligong Liu,Onisha Patel,Jennifer Mahony,Zhenjun Chen,Rangsima Reantragoon,Bronwyn S. Meehan,Hanwei Cao,Nicholas A. Williamson,Richard A. Strugnell,Douwe van Sinderen,Jeffrey Y. W. Mak,David P. Fairlie,Lars Kjer-Nielsen,Jamie Rossjohn,James McCluskey +17 more
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TLDR
It is shown that MAIT-cell activation requires key genes encoding enzymes that form 5-amino-6-d-ribitylaminouracil (5-A-RU), an early intermediate in bacterial riboflavin synthesis, and MR1 is able to capture, stabilize and present chemically unstable pyrimidine intermediates, which otherwise convert to lumazines, as potent antigens to MAIT cells.Abstract:
T cells discriminate between foreign and host molecules by recognizing distinct microbial molecules, predominantly peptides and lipids. Riboflavin precursors found in many bacteria and yeast also selectively activate mucosal-associated invariant T (MAIT) cells, an abundant population of innate-like T cells in humans. However, the genesis of these small organic molecules and their mode of presentation to MAIT cells by the major histocompatibility complex (MHC)-related protein MR1 (ref. 8) are not well understood. Here we show that MAIT-cell activation requires key genes encoding enzymes that form 5-amino-6-d-ribitylaminouracil (5-A-RU), an early intermediate in bacterial riboflavin synthesis. Although 5-A-RU does not bind MR1 or activate MAIT cells directly, it does form potent MAIT-activating antigens via non-enzymatic reactions with small molecules, such as glyoxal and methylglyoxal, which are derived from other metabolic pathways. The MAIT antigens formed by the reactions between 5-A-RU and glyoxal/methylglyoxal were simple adducts, 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU) and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), respectively, which bound to MR1 as shown by crystal structures of MAIT TCR ternary complexes. Although 5-OP-RU and 5-OE-RU are unstable intermediates, they became trapped by MR1 as reversible covalent Schiff base complexes. Mass spectra supported the capture by MR1 of 5-OP-RU and 5-OE-RU from bacterial cultures that activate MAIT cells, but not from non-activating bacteria, indicating that these MAIT antigens are present in a range of microbes. Thus, MR1 is able to capture, stabilize and present chemically unstable pyrimidine intermediates, which otherwise convert to lumazines, as potent antigens to MAIT cells. These pyrimidine adducts are microbial signatures for MAIT-cell immunosurveillance.read more
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The gut-liver axis in liver disease: Pathophysiological basis for therapy.
TL;DR: The identification of the elements of the gut-liver axis primarily damaged in each chronic liver disease offers possibilities to intervention.
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References
More filters
Journal ArticleDOI
Coot: model-building tools for molecular graphics.
Paul Emsley,Kevin Cowtan +1 more
TL;DR: CCP4mg is a project that aims to provide a general-purpose tool for structural biologists, providing tools for X-ray structure solution, structure comparison and analysis, and publication-quality graphics.
Journal ArticleDOI
The CCP4 suite: programs for protein crystallography
TL;DR: The CCP4 (Collaborative Computational Project, number 4) program suite is a collection of programs and associated data and subroutine libraries which can be used for macromolecular structure determination by X-ray crystallography.
Journal ArticleDOI
Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines.
TL;DR: The use of a tetracycline-resistance transposon, Tn10 (refs 5, 6), inserted in gene aroA to produce non-reverting, aromatic-requiring derivatives of virulent S. typhimurium strains were virtually non-virulent; their use as live vaccines conferred excellent protection against challenge with a virulent strain.
Journal ArticleDOI
Solving structures of protein complexes by molecular replacement with Phaser.
TL;DR: Four case studies in using maximum-likelihood molecular replacement, as implemented in the program Phaser, to solve structures of protein complexes are described.
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