Sulfated bile acid is a host-derived ligand for MAIT cells

Journal article

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize bacterial riboflavin–based metabolites as activating antigens. Although MAIT cells are found in tissues, it is unknown whether any host tissue–derived antigens exist. Here, we report that a sulfated bile acid, cholic acid 7-sulfate (CA7S), binds the nonclassical MHC class I protein MR1 and is recognized by MAIT cells. CA7S is a host-derived metabolite whose levels were reduced by more than 98% in germ-free mice. Deletion of the sulfotransferase 2a family of enzymes (Sult2a1-8) responsible for CA7S synthesis reduced the number of thymic MAIT cells in mice. Moreover, recognition of CA7S induced MAIT cell survival and the expression of a homeostatic gene signature. By contrast, recognition of a previously described foreign antigen, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), drove MAIT cell proliferation and the expression of inflammatory genes. Thus, CA7S is an endogenous antigen for MAIT cells, which promotes their development and function.

Authors: Ito, E; Inuki, S; Izumi, Y; Takahashi, M; Dambayashi, Y

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: American Association for the Advancement of Science
• Journal: Science Immunology
• Volume: 9
• Issue: 91
• Article number: eade6924
• Publication date: 2024-01-26
• Acceptance date: 2024-01-03
• DOI: 10.1126/sciimmunol.ade6924
• EISSN: 2470-9468
• Pmid: 38277465
• Language: English
• Keywords: bile acids and salts; antigens; mice; sulfates; ligands; minor histocompatibility antigens; mucosal-associated invariant T cells