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| Item Type: | Article |
|---|---|
| Title: | DNA origami demonstrate the unique stimulatory power of single pMHCs as T cell antigens |
| Creators Name: | Hellmeier, J., Platzer, R., Eklund, A.S., Schlichthaerle, T., Karner, A., Motsch, V., Schneider, M.C., Kurz, E., Bamieh, V., Brameshuber, M., Preiner, J., Jungmann, R., Stockinger, H., Schütz, G.J., Huppa, J.B. and Sevcsik, E. |
| Abstract: | 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. |
| Keywords: | DNA Origami, Nanobiotechnology, T Cell Activation, pMHC, Serial Engagemen, Animals, Mice |
| Source: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Volume: | 118 |
| Number: | 4 |
| Page Range: | e2016857118 |
| Date: | 26 January 2021 |
| Official Publication: | https://doi.org/10.1073/pnas.2016857118 |
| PubMed: | View item in PubMed |
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