期刊
SCIENCE ADVANCES
卷 7, 期 24, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abc1640
关键词
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资金
- Multidisciplinary Research Grant-The Faculty of Health Science in Ben-Gurion University of the Negev
- Israel Science Foundation [1401/15, 2058/18]
- COST Action [CA15126]
- German Science Foundation [SM 289/8-1, AOBJ: 652939]
- China Scholarship Council (CSC) [201806185038]
- Israel Ministry of Science and Technology
- Israel Scholarship Education Foundation (ISEF)
- Ariane de Rothschild Women's Doctoral scholarships program
- Conseil Regional d'Aquitaine
- GIS-IBiSA
- Cellule Hotels a Projets of the CNRS
The study revealed that a 40-nm gap between activating and inhibitory ligands provided optimal inhibitory conditions. This nanoengineered multifunctional platform offers important insights into the spatial mechanism of inhibitory immune checkpoints.
The role of juxtaposition of activating and inhibitory receptors in signal inhibition of cytotoxic lymphocytes remains strongly debated. The challenge lies in the lack of tools that allow simultaneous spatial manipulation of signaling molecules. To circumvent this, we produced a nanoengineered multifunctional platform with molecular-scale spatial control of ligands, which was applied to elucidate KIR2DL1-mediated inhibition of NKG2D signaling-receptors of natural killer cells. This platform was conceived by bimetallic nanodot patterning with molecular-scale registry, followed by a ternary functionalization with distinct moieties. We found that a 40-nm gap between activating and inhibitory ligands provided optimal inhibitory conditions. Supported by theoretical modeling, we interpret these findings as a consequence of the size mismatch and conformational flexibility of ligands in their spatial interaction. This highly versatile approach provides an important insight into the spatial mechanism of inhibitory immune checkpoints, which is essential for the rational design of future immunotherapies.
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