bims-maitce 2024-01-28 papers

Issue of 2024‒01‒28
four papers selected by
Andy E. Hogan, Maynooth University

Sci Immunol. 2024 Jan 26. 9(91): eade6924

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

Emi Ito, Shinsuke Inuki, Yoshihiro Izumi, Masatomo Takahashi, Yuki Dambayashi, Lisa Ciacchi, Wael Awad, Ami Takeyama, Kensuke Shibata, Shotaro Mori, Jeffrey Y W Mak, David P Fairlie, Takeshi Bamba, Eri Ishikawa, Masamichi Nagae, Jamie Rossjohn, Sho Yamasaki.

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.

DOI: https://doi.org/10.1126/sciimmunol.ade6924

J Immunol. 2024 Jan 26. pii: ji2300609. [Epub ahead of print]

Multiple Isomers of Photolumazine V Bind MR1 and Differentially Activate MAIT Cells.

Jason R Krawic, Nicole A Ladd, Meghan Cansler, Curtis McMurtrey, Jordan Devereaux, Aneta Worley, Tania Ahmed, Cara Froyd, Corinna A Kulicke, Gwendolyn Swarbrick, Aaron Nilsen, David M Lewinsohn, Erin J Adams, William Hildebrand.

In response to microbial infection, the nonclassical Ag-presenting molecule MHC class I-related protein 1 (MR1) presents secondary microbial metabolites to mucosal-associated invariant T (MAIT) cells. In this study, we further characterize the repertoire of ligands captured by MR1 produced in Hi5 (Trichoplusia ni) cells from Mycobacterium smegmatis via mass spectrometry. We describe the (to our knowledge) novel MR1 ligand photolumazine (PL)V, a hydroxyindolyl-ribityllumazine with four isomers differing in the positioning of a hydroxyl group. We show that all four isomers are produced by M. smegmatis in culture and that at least three can induce MR1 surface translocation. Furthermore, human MAIT cell clones expressing distinct TCR β-chains differentially responded to the PLV isomers, demonstrating that the subtle positioning of a single hydroxyl group modulates TCR recognition. This study emphasizes structural microheterogeneity within the MR1 Ag repertoire and the remarkable selectivity of MAIT cell TCRs.

DOI: https://doi.org/10.4049/jimmunol.2300609

Biomedicines. 2024 Jan 09. pii: 137. [Epub ahead of print]12(1):

Mice Generated with Induced Pluripotent Stem Cells Derived from Mucosal-Associated Invariant T Cells.

Chie Sugimoto, Hiroyoshi Fujita, Hiroshi Wakao.

The function of mucosal-associated invariant T (MAIT) cells, a burgeoning member of innate-like T cells abundant in humans and implicated in many diseases, remains obscure. To explore this, mice with a rearranged T cell receptor (TCR) α or β locus, specific for MAIT cells, were generated via induced pluripotent stem cells derived from MAIT cells and were designated Vα19 and Vβ8 mice, respectively. Both groups of mice expressed large numbers of MAIT cells. The MAIT cells from these mice were activated by cytokines and an agonist to produce IFN-γ and IL-17. While Vβ8 mice showed resistance in a cancer metastasis model, Vα19 mice did not. Adoptive transfer of MAIT cells from the latter into the control mice, however, recapitulated the resistance. These mice present an implication for understanding the role of MAIT cells in health and disease and in developing treatments for the plethora of diseases in which MAIT cells are implicated.

Keywords: MAIT cells; anti-metastatic activity; chimeric mice; iPS cells; rearranged TCR

DOI: https://doi.org/10.3390/biomedicines12010137