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| Item Type: | Article |
|---|---|
| Title: | DNA origami demonstrate the unique stimulatory power of single pMHCs as T cell antigens |
| Creators: |
Hellmeier, J.  ORCID: https://orcid.org/0000-0002-7153-9121, Platzer, R., Eklund, A.S. ORCID: https://orcid.org/0000-0003-1047-2100, Schlichthaerle, T. ORCID: https://orcid.org/0000-0003-4444-2575, Karner, A., Motsch, V. ORCID: https://orcid.org/0000-0002-4860-4247, Schneider, M.C. ORCID: https://orcid.org/0000-0002-3771-8353, Kurz, E., Bamieh, V., Brameshuber, M. ORCID: https://orcid.org/0000-0001-8672-2255, Preiner, J. ORCID: https://orcid.org/0000-0002-6755-6543, Jungmann, R. ORCID: https://orcid.org/0000-0003-4607-3312, Stockinger, H. ORCID: https://orcid.org/0000-0001-6404-4430, Schütz, G.J. ORCID: https://orcid.org/0000-0003-1542-1089, Huppa, J.B. ORCID: https://orcid.org/0000-0003-2634-8198 and Sevcsik, E. ORCID: https://orcid.org/0000-0002-2155-1675
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| 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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