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6-FP

scTCR
The MAIT TCR is restricted by the MHC class I–related molecule MR1. MR1 is a monomorphic Ag-presenting molecule that is highly conserved across mammals. Although the MR1 transcript is expressed widely, cell surface expression of MR1 is very low/absent, thereby indicating that other factors, including Ag supply, can determine the level of MR1 that egresses to the cell membrane. Recently, it has been established that MR1 can bind vitamin B–based precursors and derivatives that originate from folic acid (vitamin B9) and riboflavin (vitamin B2) biosynthesis. Specifically, MR1 can present 6-formylpterin (6-FP), a naturally occurring photo-degradation product of folic acid, and a series of ribityllumazines, including 6,7-dimethyl-8-d-ribityllumazine (RL-6,7-DiMe), 6-methyl-7-hydroxy-8-d-ribityllumazine (RL-6-Me-7-OH), 5-(2-oxoethylideneamino)-6-d-ribitylaminouracil (5-OE-RU), and 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU). The MR1 Ag-binding cleft is ideally disposed to bind to these small organic metabolites, with the ligands being closely sequestered by an aromatic cradle within MR1, whereupon some of the ligands can form a covalent bond (Schiff base) with MR1.

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