作者: Lars Kjer-Nielsen , Alexandra J Corbett , Zhenjun Chen , Ligong Liu , Jeffrey YW Mak
DOI: 10.1111/IMCB.12057
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摘要: Mucosal Associated Invariant T (MAIT) cells are restricted by the monomorphic MHC class I-like molecule, MHC-related protein-1 (MR1). Until 2012, origin of MAIT cell antigens (Ags) was unknown, although it established that could be activated a broad range bacteria and yeasts, possibly suggesting conserved Ag. Using combination protein chemistry, mass spectrometry, cellular biology, structural biology we discovered ligands derived from folic acid (vitamin B9) an intermediate in microbial biosynthesis riboflavin B2). While folate derivative 6-formylpterin (6-FP) generally inhibited activation, two pathway derivatives, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU), were potent agonists. Other intermediates derivatives synthesis displayed weak or no activation. Collectively, these studies revealed addition to peptide lipid-based Ags, small molecule natural product metabolites also can activate expressing αβ receptors, here recount this discovery. This article is protected copyright. All rights reserved.