T-cell activation by transitory neo-antigens derived from distinct microbial pathways
Alexandra J Corbett, Sidonia BG Eckle, Richard W Birkinshaw, Ligong Liu, Onisha Patel, Jennifer Mahony, Zhenjun Chen, Rangsima Reantragoon, Bronwyn Meehan, Hanwei Cao, Nicholas A Williamson, Richard A Strugnell, Douwe Van Sinderen, Jeffrey YW Mak, David P Fairlie, Lars Kjer-Nielsen, Jamie Rossjohn, James McCluskey
NATURE | NATURE PUBLISHING GROUP | Published : 2014
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...View full abstract
Awarded by Science Foundation Ireland (SFI)
Awarded by NHMRC
We thank the staff of the Monash crystallization facility and the Australian Synchrotron for assistance with crystallization and data collection, respectively, and M. J. McConville, P. O'Donnell and C.-S. Ang from the University of Melbourne Bio21 Institute mass spectrometry platform for assistance with mass spectrometry experiments. The Australian Research Council (ARC), a Program Grant and Project Grant of the National Health and Medical Research Council of Australia (NHMRC) supported this research; D. V. S. is a recipient of a Science Foundation Ireland (SFI) Principal Investigator award (ref. no. 08/IN.1/B1909); O.P. was supported by an ARC Future Fellowship; D. P. F. was supported by an NHMRC Senior Principal Research Fellowship (1027369); J. R. was supported by an NHMRC Australia Fellowship.