Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario.
Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario; Department of Biological Sciences, University of Toronto Scarborough, Toronto, Ontario; Department of Immunology, University of Toronto, Toronto, Ontario.
Biophys J. 2024 Aug 6;123(15):2211-2223. doi: 10.1016/j.bpj.2023.10.013. Epub 2023 Oct 14.
The immune response is orchestrated by elaborate protein interaction networks that interweave ligand-mediated receptor reorganization with signaling cascades. While the biochemical processes have been extensively investigated, delineating the biophysical principles governing immune receptor activation has remained challenging due to design limitations of traditional ligand display platforms. These constraints have been overcome by advances in DNA origami nanotechnology, enabling unprecedented control over ligand geometry on configurable scaffolds. It is now possible to systematically dissect the independent roles of ligand stoichiometry, spatial distribution, and rigidity in immune receptor activation, signaling, and cooperativity. In this review, we highlight pioneering efforts in manipulating the ligand presentation landscape to understand immune receptor triggering and to engineer functional immune responses.
免疫反应是由精细的蛋白质相互作用网络协调的，这些网络将配体介导的受体重排与信号级联交织在一起。虽然生化过程已经得到了广泛的研究，但由于传统配体展示平台的设计限制，阐明控制免疫受体激活的生物物理原理仍然具有挑战性。DNA 折纸纳米技术的进步克服了这些限制，使得在可配置支架上对配体几何形状进行前所未有的控制成为可能。现在可以系统地剖析配体计量、空间分布和刚性在免疫受体激活、信号转导和协同作用中的独立作用。在这篇综述中，我们强调了操纵配体呈现景观以理解免疫受体触发和工程功能性免疫反应的开创性工作。
