Journal article

Mucosal-associated invariant T-cell activation and accumulation after in vivo infection depends on microbial riboflavin synthesis and co-stimulatory signals

Z Chen, H Wang, C D'Souza, S Sun, L Kostenko, SBG Eckle, BS Meehan, DC Jackson, RA Strugnell, H Cao, N Wang, DP Fairlie, L Liu, DI Godfrey, J Rossjohn, J McCluskey, AJ Corbett



Despite recent breakthroughs in identifying mucosal-associated invariant T (MAIT) cell antigens (Ags), the precise requirements for in vivo MAIT cell responses to infection remain unclear. Using major histocompatibility complex-related protein 1 (MR1) tetramers, the MAIT cell response was investigated in a model of bacterial lung infection employing riboflavin gene-competent and -deficient bacteria. MAIT cells were rapidly enriched in the lungs of C57BL/6 mice infected with Salmonella Typhimurium, comprising up to 50% of αβ-T cells after 1 week. MAIT cell accumulation was MR1-dependent, required Ag derived from the microbial riboflavin synthesis pathway, and did not occur in response to synt..

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Awarded by National Health and Medical Research Council of Australia (NHMRC)

Funding Acknowledgements

This research was supported by Program Grants 1016629 and 606788 and Project Grant 1083942 from the National Health and Medical Research Council of Australia (NHMRC). J.R. was supported by an NHMRC Australia Fellowship, D.P.F. was supported by an NHMRC Senior Principal Research Fellowship, and D.C.J. and D.I.G. are supported by NHMRC Research Fellowships. H.W. is supported by a Melbourne International Engagement Award (University of Melbourne). C.D'S. is supported by a Melbourne International Research Scholarship and a Melbourne International Fee Remission Scholarship (University of Melbourne). We thank Dr Wei-Jen Chua and Dr Ted Hansen for their kind provision of 8F2.F9 and 26.5 mAbs.