A Stable Isopterin Mimic of a Potent Bacterial Stimulant of T Cells

Abstract

Mucosal-associated invariant T cells (MAIT cells) are innate-like immune cells (T lymphocytes) that protect against bacterial infections. They are potently activated by the microbial metabolite 5-(2-oxopropylideneamino)-d-ribitylaminouracil (5-OP-RU), which bonds covalently to an amine of a specific lysine residue of the antigen-presenting protein MR1 to form an imine (Schiff base). However, 5-OP-RU undergoes rapid degradative intramolecular cyclisation in water, and more robust analogues are needed for therapeutic applications. Here, inspired by the structural similarities between 5-OP-RU and 6-formylpterin, a water-stable covalent MR1 ligand that does not activate MAIT cells, we describe t..