Magic™ Humanized TIM-3 Immune Checkpoint Knock-In Mice

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  • Published date: October 30, 2019
    • Shirley, New York, United States

T-cell inhibitory receptor TIM-3 (T-cell immunoglobulin and mucin domain 3) is expressed on Th1, Th17, CD8+ T cells and it is a T cell inhibitory receptor. TIM family is a kind of membrane protein, which contains three parts: a variable immunoglobulin domain (IgV), a glycosylated mucin domain of varying length in the extracellular region, and a single transmembrane domain. TIM-3 has four relevant ligands, which include galectin-9 (Gal-9), high mobility group protein B1 (HMGB1), carcinoembryonic antigen cell adhesion molecule 1 (Ceacam-1), and phosphatidylserine (PtdSer). Gal-9 can bind to TIM-3 and incite an influx of calcium to the intracellular region of Th1 cells, inducing T cell apoptosis. The interaction of PtdSer and TIM3 facilitates the clearance of apoptotic bodies and also promotes the cross-presentation of antigens by dendritic cells (DCs). HMGB1 is the key ligand that activates of normal dendritic cells (DCs) and that TIM-3 inhibit the role of HMGB1 in tumor-infiltrating DCs. The interaction between Ceacam-1 and TIM-3 is functioned as a negative regulator of T cell responses.

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Jerry Carter
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