Poster Presentation CD1-MR1 2024

Establishment of an MR1-presentation reporter screening system to identify MAIT cell modulators (#100)

Takuro Matsuoka 1 , Akira Hattori 1 , Shinya Oishi 1 , Mitsugu Araki 2 , Biao Ma 3 , Toshiki Fujii 1 , Norihito Arichi 1 , Yasushi Okuno 2 3 , Hideaki Kakeya 1 , Sho Yamasaki 4 , Hiroaki Ohno 1 , Shinsuke Inuki 1
  1. Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto
  2. Graduate School of Medicine, Kyoto University, Kyoto
  3. RIKEN Center for Computational Science, Kobe
  4. RIMD / IFReC, Osaka University, Suita

Mucosal-associated invariant T (MAIT) cells are a subtype of innate-like T cells that are modulated by ligands presented on MHC class I-related proteins (MR1). These cells have attracted attention as potential drug targets because of their involvement in the initial response to infection and various disorders. Consequently, the identification of MR1 ligands capable of modulating MAIT cells, encompassing both endogenous and exogenous ligands, holds significant importance. Herein, we constructed an MR1 ligand screening method based on the detection of the cell surface levels of MR1 as an indicator. In this screening system, the HiBiT-LgBiT (split-luciferase) system was used to detect an increase in the cell surface levels of MR1, enabling a rapid and simple evaluation of the complex formation of MR1 with ligands in the cellular milieu. Using this screening system, we identified phenylpropanoid derivatives as MR1 ligands, including coniferyl aldehyde, which have an ability to inhibit the MR1–MAIT cell axis. Further structure-activity relationship study and binding mode analysis of coniferyl aldehyde analogs revealed the key structural features of ligands required for MR1 recognition. The screening system developed in this study will contribute to identifying a broad range of MR1 ligands, with implications for our understanding of MAIT cell functions.

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