5-amino-6-(D-ribitylamino)uracil

5-Amino-6-(D-ribitylamino)uracil (5-A-RU) is a precursor of bacterial Riboflavin. 5-Amino-6-(D-ribitylamino)uracil is a mucosal-associated invariant T (MAIT) cells activator. 5-Amino-6-(D-ribitylamino)uracil forms potent MAIT-activating antigens via non-enzymatic reactions with small molecules, such as glyoxal and methylglyoxal, which are derived from other metabolic pathways[1][2][3].

Signaling Pathways >> Others >> Others

Research Areas >> Inflammation/Immunology

The MAIT antigens formed by the reactions between 5-Amino-6-(D-ribitylamino)uracil and glyoxal/methylglyoxal are simple adducts, 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU) and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), respectively, which bound to MR1 as shown by crystal structures of MAIT TCR ternary complexes[1]. 5-A-RU presents in diverse bacteria and yeast as well as plants. 5-A-RU plays an important role in MAIT cell activation, MR1 could not be refolded efficiently with 5-ARU alone. 5-A-RU is a precursor for MAIT cell ligand[2]. 5-A-RU can react extemporaneously with glyoxal and methylglyoxal to generate pyrimidine adducts that activate mouse MAIT cells from STg (iVa19) and DTg (iVa19Vb6) animals[3].

5-A-RU (100 nM; i.p.; 18 hours) and methylglyoxal (MeG) are mixed extemporaneously, MAIT cells are activated in iVa19 Cα-/- Tg mice (generated on the C57BL/6 background)[3].

[1]. Corbett AJ, et al. T-cell activation by transitory neo-antigens derived from distinct microbial pathways. Nature. 2014 May 15;509(7500):361-5.

[2]. Eckle SB, et al. Recognition of Vitamin B Precursors and Byproducts by Mucosal Associated Invariant T Cells.

[3]. Soudais C, et al. In Vitro and In Vivo Analysis of the Gram-Negative Bacteria-Derived Riboflavin PrecursorDerivatives Activating Mouse MAIT Cells. J Immunol. 2015 May 15;194(10):4641-9.