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Development of Novel Ligands That Modulate Innate-Like T Cells

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New Tide of Natural Product Chemistry

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Abstract

Innate-like T cells function as a bridge between innate and acquired immunity and play an important role in the initial immune response toward infection. Natural killer T (NKT) cells or mucosal-associated invariant T (MAIT) cells are classified as innate-like T cells, which are activated by the T cell receptor recognition of ligands present on MHC-like molecules (CD1d, MR1). Activated NKT or MAIT cells mediate various immune responses via cytokine production. Through the modification of natural ligands using synthetic organic chemistry, the author has been elucidating the molecular recognition mechanisms of NKT or MAIT cell activation and developing chemical tools or lead compounds for drug discovery. In this chapter, our recent structure–activity relationship (SAR) studies for developing novel innate-like T cell modulators would be described.

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Acknowledgements

The author would like to express his sincere and wholehearted appreciation to Professor Hiroaki Ohno (Graduate School of Pharmaceutical Sciences, Kyoto University) and Professor Yukari Fujimoto (Department of Chemistry, Faculty of Science and Technology, Keio University) for their kind guidance, constructive discussions and constant encouragement during this study. The author would like to thank Dr. Osamu Ichihara and Mr. Daisuke Yoshidome (Schrödinger K. K.) for their support with MD simulation, and Professor. Sho Yamasaki (Research Institute for Microbial Diseases, Osaka University) for his professional guidance on the MAIT cell activation assay. The author is grateful to all the colleagues of the Department of Bioorganic Medicinal Chemistry (Graduate School of Pharmaceutical Sciences, Kyoto University) and the laboratory of Biomolecular Chemistry (Department of Chemistry, Faculty of Science and Technology, Keio University) for their valuable comments and their assistance and cooperation in various experiments.

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  1. Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshidashimoadachi-Cho, Sakyo-Ku, Kyoto, 606-8501, Japan

    Shinsuke Inuki

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  1. Chiba University, Chiba, Japan

    Hayato Ishikawa

  2. Chiba University, Chiba, Japan

    Hiromitsu Takayama

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Inuki, S. (2023). Development of Novel Ligands That Modulate Innate-Like T Cells. In: Ishikawa, H., Takayama, H. (eds) New Tide of Natural Product Chemistry. Springer, Singapore. https://doi.org/10.1007/978-981-99-1714-3_17

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