Spatial Regulation of T-Cell Signaling by Programmed Death-Ligand 1 on Wireframe DNA Origami Flat Sheets.

ABSTRACT: Programmed Death-1 (PD-1) is a coinhibitory receptor expressed on activated T cells that suppresses T-cell signaling and effector functions. It has been previously shown that binding to its ligand PD-L1 induces a spatial reorganization of PD-1 receptors into microclusters on the cell membrane. However, the roles of the spatial organization of PD-L1 on PD-1 clustering and T-cell signaling have not been elucidated. Here, we used DNA origami flat sheets to display PD-L1 ligands at defined nanoscale distances and investigated their ability to inhibit T-cell activation in vitro. We found that DNA origami flat sheets modified with CD3 and CD28 activating antibodies (FS-α-CD3-CD28) induced robust T-cell activation. Co-treatment with flat sheets presenting PD-L1 ligands separated by ∼200 nm

SUBMITTER: Fang T 

PROVIDER: S-EPMC7905882 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature