Journal article
MR1 presents vitamin B6-related compounds for recognition by MR1-reactive T cells
MP McInerney, W Awad, MNT Souter, Y Kang, CJH Wang, KCY Poa, MR Abdelaal, NH Le, CM Shepherd, C McNeice, LJ Meehan, AG Nelson, JM Raynes, JYW Mak, J McCluskey, Z Chen, CS Ang, DP Fairlie, JL Nours, PT Illing Show all
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2024
Abstract
The major histocompatibility complex class I related protein (MR1) presents microbially derived vitamin B2 precursors to mucosal-associated invariant T (MAIT) cells. MR1 can also present other metabolites to activate MR1-restricted T cells expressing more diverse T cell receptors (TCRs), some with anti-tumor reactivity. However, knowledge of the range of the antigen(s) that can activate diverse MR1-reactive T cells remains incomplete. Here, we identify pyridoxal (vitamin B6) as a naturally presented MR1 ligand using unbiased mass spectrometry analyses of MR1-bound metabolites. Pyridoxal, and the related compound, pyridoxal 5-phosphate bound to MR1 and enabled cell surface upregulation of wil..
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Grants
Awarded by University of Melbourne
Funding Acknowledgements
We acknowledge the Monash Biomedical Proteomics Facility, Monash University, for the provision of instrumentation, training, and technical support; Monash University FlowCore Facility forflow cytometry instrumentation, technical support, and sorting of cells; and the use of the servicesand facilities of Micromon Genomics at Monash University. We acknowledge the Melbourne Cytometry Platform (Peter Doherty Institute node) for provision of flow cytometry services and the Bio21 Institute Proteomics and Mass Spectrometry Facility. We thank the staff at the Monash Macromolecular Crystallization Facility. This research was undertaken in part using the MX2 beamline at the Australian Synchrotron, part of Australian Nuclear Science and Technology Organisation, and used the Australian Cancer Research Foundation detector. We acknowledge Austin Health and the Austin Health Researchers (Varun J. Sharma, Aly Fayed, Graham Starkey, Rohit D'Costa, Claire L. Gordon) for provision of splenocytes as part of the Australian Donation and Transplantation Biobank (ADTB) . We gratefully acknowledge the generosity of the deceased organ donors and their families in providing valuable samples to the ADTB. This work was supported by a NIH (R01 AI148407-01A1 toJ.M.,J.R., and D.P.F.) ; Australian Research Council (ARC) Discovery Grants DP220102401 to A.W.P. and J.R. and DP240102905 to J.M., M.N.T.S., and Z.C., an ARC Centre of Excellence Grant (CE200100012) to D.P.F, and a University of Melbourne Early Career Researcher Grant to M.N.T.S. W.A. is supported by an ARC Discovery Early Career Researcher Award (DE220101491) .J.R.,A.W.P., D.P.F., and J.M. are supported by Australian National Health and Medical Research Council Investigator Awards (2008981, 2016596, 2009551, and 2008616, respectively) .