Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells

Keller, Andrew N., Eckle, Sidonia B. G., Xu, Weijun, Liu, Ligong, Hughes, Victoria A., Mak, Jeffrey Y. W. , Meehan, Bronwyn S., Pediongco, Troi, Birkinshaw, Richard W. , Chen, Zhenjun, Wang, Huimeng, D'Souza, Criselle, Kjer-Nielsen, Lars, Gherardin, Nicholas A., Godfrey, Dale I., Kostenko, Lyudmila, Corbett, Alexandra J. , Purcell, Anthony W., Fairlie, David P., McCluskey, James and Rossjohn, Jamie (2017) Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells. Nature Immunology, . doi:10.1038/ni.3679


Author Keller, Andrew N.
Eckle, Sidonia B. G.
Xu, Weijun
Liu, Ligong
Hughes, Victoria A.
Mak, Jeffrey Y. W.
Meehan, Bronwyn S.
Pediongco, Troi
Birkinshaw, Richard W.
Chen, Zhenjun
Wang, Huimeng
D'Souza, Criselle
Kjer-Nielsen, Lars
Gherardin, Nicholas A.
Godfrey, Dale I.
Kostenko, Lyudmila
Corbett, Alexandra J.
Purcell, Anthony W.
Fairlie, David P.
McCluskey, James
Rossjohn, Jamie
Title Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells
Journal name Nature Immunology   Check publisher's open access policy
ISSN 1529-2916
1529-2908
Publication date 2017-02-06
Sub-type Article (original research)
DOI 10.1038/ni.3679
Open Access Status Not yet assessed
Total pages 14
Place of publication New York, United States
Publisher Nature Publishing Group
Collection year 2018
Language eng
Formatted abstract
The major-histocompatibility-complex-(MHC)-class-I-related molecule MR1 can present activating and non-activating vitamin-B-based ligands to mucosal-associated invariant T cells (MAIT cells). Whether MR1 binds other ligands is unknown. Here we identified a range of small organic molecules, drugs, drug metabolites and drug-like molecules, including salicylates and diclofenac, as MR1-binding ligands. Some of these ligands inhibited MAIT cells ex vivo and in vivo, while others, including diclofenac metabolites, were agonists. Crystal structures of a T cell antigen receptor (TCR) from a MAIT cell in complex with MR1 bound to the non-stimulatory and stimulatory compounds showed distinct ligand orientations and contacts within MR1, which highlighted the versatility of the MR1 binding pocket. The findings demonstrated that MR1 was able to capture chemically diverse structures, spanning mono- and bicyclic compounds, that either inhibited or activated MAIT cells. This indicated that drugs and drug-like molecules can modulate MAIT cell function in mammals.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Published online 6 February 2017

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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Created: Mon, 13 Mar 2017, 21:25:23 EST by Mr Jeffrey Mak on behalf of Learning and Research Services (UQ Library)