Journal article
A molecular basis underpinning the T cell receptor heterogeneity of mucosal-associated invariant T cells
SBG Eckle, RW Birkinshaw, L Kostenko, AJ Corbett, HEG McWilliam, R Reantragoon, Z Chen, NA Gherardin, T Beddoe, L Liu, O Patel, B Meehan, DP Fairlie, JA Villadangos, DI Godfrey, L Kjer-Nielsen, J McCluskey, J Rossjohn
Journal of Experimental Medicine | Published : 2014
DOI: 10.1084/jem.20140484
Abstract
Mucosal-associated invariant T (MAIT) cells express an invariant T cell receptor (TCR) α-chain (TRAV1-2 joined to TRAJ33, TRAJ20, or TRAJ12 in humans), which pairs with an array of TCR β-chains. MAIT TCRs can bind folate- and riboflavin-based metabolites restricted by the major histocompatibility complex (MHC)-related class I-like molecule, MR1. However, the impact of MAIT TCR and MR1-ligand heterogeneity on MAIT cell biology is unclear. We show how a previously uncharacterized MR1 ligand, acetyl-6-formylpterin (Ac-6-FP), markedly stabilized MR1, potently up-regulated MR1 cell surface expression, and inhibited MAIT cell activation. These enhanced properties of Ac-6-FP were attributable to st..
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Funding Acknowledgements
This research was supported by the National Health and Medical Research Council of Australia (NHMRC) and the Australian Research Council. We thank Ted Hansen for the 26.5 Mab. R. Reantragoon was supported by the Faculty of Medicine, Chulalongkorn University and Chulalongkorn Hospital, Thai Red Cross Society scholarships. N.A. Gherardin was supported by a Leukemia Foundation postgraduate scholarship. D.P. Fairlie and D.I. Godfrey were supported by NHMRC Senior Principal Research Fellowships; O. Patel was supported by an ARC Future Fellowship; and J. Rossjohn was supported by an NHMRC Australia Fellowship.