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T cells detect with their T cell antigen receptors (TCRs) the presence of rare agonist peptide/MHC complexes (pMHCs) on the surface of antigen-presenting cells (APCs). How extracellular ligand binding triggers intracellular signaling is poorly understood, yet spatial antigen arrangement on the APC surface has been suggested to be a critical factor. To examine this, we engineered a biomimetic interface based on laterally mobile functionalized DNA origami platforms, which allow for nanoscale control over ligand distances without interfering with the cell-intrinsic dynamics of receptor clustering. When targeting TCRs via stably binding monovalent antibody fragments, we found the minimum signaling unit promoting efficient T cell activation to consist of two antibody-ligated TCRs within a distance of 20 nm. In contrast, transiently engaging antigenic pMHCs stimulated T cells robustly as well-isolated entities. These results identify pairs of antibody-bound TCRs as minimal receptor entities for effective TCR triggering yet validate the exceptional stimulatory potency of single isolated pMHC molecules.

Original publication




Journal article


Proc Natl Acad Sci U S A

Publication Date





DNA origami, T cell activation, nanobiotechnology, pMHC, serial engagement, Animals, Antigen-Presenting Cells, CD4-Positive T-Lymphocytes, DNA, Gene Expression, Ligands, Lipid Bilayers, Lymphocyte Activation, Major Histocompatibility Complex, Mice, Nucleic Acid Conformation, Phosphatidylcholines, Primary Cell Culture, Protein Binding, Receptors, Antigen, T-Cell, Signal Transduction, Single-Chain Antibodies, Spleen