MR1 presents microbial vitamin B metabolites to MAIT cells

作者：Kjer-Nielsen, Lars; Patel, Onisha; Corbett, Alexandra J.; Le Nours, Jerome; Meehan, Bronwyn; Liu, Ligong; Bhati, Mugdha; Chen, Zhenjun; Kostenko, Lyudmila; Reantragoon, Rangsima; Williamson, Nicholas A.; Purcell, Anthony W.; Dudek, Nadine L.; McConville, Malcolm J.; O'Hair, Richard A. J.; Khairallah, George N.; Godfrey, Dale I.; Fairlie, David P.; Rossjohn, Jamie; McCluskey, James^*

来源：Nature, 2012, 491(7426): 717-+.

DOI：10.1038/nature11605

• INVARIANT T-CELLS
• CRYSTAL-STRUCTURE
• ANTIGEN PRESENTATION
• SELECTION

Antigen-presenting molecules, encoded by the major histocompatibility complex (MHC) and CD1 family, bind peptide- and lipid-based antigens, respectively, for recognition by T cells. Mucosal-associated invariant T (MAIT) cells are an abundant population of innate-like T cells in humans that are activated by an antigen(s) bound to the MHC class I-like molecule MR1. Although the identity of MR1-restricted antigen(s) is unknown, it is present in numerous bacteria and yeast. Here we show that the structure and chemistry within the antigen-binding cleft of MR1 is distinct from the MHC and CD1 families. MR1 is ideally suited to bind ligands originating from vitamin metabolites. The structure of MR1 in complex with 6-formyl pterin, a folic acid (vitamin B9) metabolite, shows the pterin ring sequestered within MR1. Furthermore, we characterize related MR1-restricted vitamin derivatives, originating from the bacterial riboflavin (vitamin B2) biosynthetic pathway, which specifically and potently activate MAIT cells. Accordingly, we show that metabolites of vitamin B represent a class of antigen that are presented by MR1 for MAIT-cell immunosurveillance. As many vitamin biosynthetic pathways are unique to bacteria and yeast, our data suggest that MAIT cells use these metabolites to detect microbial infection.

• 出版日期2012-11-29