Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Current Understanding of Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) Signaling in T-Cell Biology and Disease Therapy

  • Kim, Gil-Ran (Department of Life Science, College of Natural Sciences, Hanyang University) ;
  • Choi, Je-Min (Department of Life Science, College of Natural Sciences, Hanyang University)
  • Received : 2021.12.31
  • Accepted : 2022.05.02
  • Published : 2022.08.31
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Abstract

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an immune checkpoint molecule that is mainly expressed on activated T cells and regulatory T (Treg) cells that inhibits T-cell activation and regulates immune homeostasis. Due to the crucial functions of CTLA-4 in T-cell biology, CTLA-4-targeted immunotherapies have been developed for autoimmune disease as well as cancers. CTLA-4 is known to compete with CD28 to interact with B7, but some studies have revealed that its downstream signaling is independent of its ligand interaction. As a signaling domain of CTLA-4, the tyrosine motif plays a role in inhibiting T-cell activation. Recently, the lysine motif has been shown to be required for the function of Treg cells, emphasizing the importance of CTLA-4 signaling. In this review, we summarize the current understanding of CTLA-4 biology and molecular signaling events and discuss strategies to target CTLA-4 signaling for immune modulation and disease therapy.

Keywords

Acknowledgement

This research was supported by grants from the Bio and Medical Technology Development Program (NRF-2017M3A9C8027972) and Basic Science Research Program (NRF-2019R1A2C3006155) of the National Research Foundation funded by the Korean government to J.-M.C.

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