Stabilizing short-lived Schiff base derivatives of 5-aminouracils that activate mucosal-associated invariant T cells.

ABSTRACT: Mucosal-associated invariant T (MAIT) cells are activated by unstable antigens formed by reactions of 5-amino-6-D-ribitylaminouracil (a vitamin B2 biosynthetic intermediate) with glycolysis metabolites such as methylglyoxal. Here we show superior preparations of antigens in dimethylsulfoxide, avoiding their rapid decomposition in water (t_1/2 1.5 h, 37 °C). Antigen solution structures, MAIT cell activation potencies (EC₅₀ 3-500 pM), and chemical stabilities are described. Computer analyses of antigen structures reveal stereochemical and energetic influences on MAIT cell activation, enabling design of a water stable synthetic antigen (EC₅₀ 2 nM). Like native antigens, this antigen preparation induces MR1 refolding and upregulates surface expression of human M

SUBMITTER: Mak JY 

PROVIDER: S-EPMC5344979 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature