DNA origami demonstrate the unique stimulatory power of single pMHCs as T-cell antigens

Joschka Hellmeier, Rene Platzer, Alexandra S. Eklund, Thomas Schlichthärle, Andreas Karner, Viktoria Motsch, Elke Kurz, Victor Bamieh, Mario Brameshuber, Johannes Preiner, Ralf Jungmann, Hannes Stockinger, Gerhard J. Schütz, Johannes B. Huppa, Eva Sevcsik

Research output: Working paperWorking paper/discussion paper

Abstract

T-cells detect with their T-cell antigen receptors (TCRs) the presence of rare peptide/MHC complexes (pMHCs) on the surface of antigen presenting cells (APCs). How they convert a biochemical interaction into a signaling response is poorly understood, yet indirect evidence pointed to the spatial antigen arrangement on the APC surface as 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. We found that the minimum signaling unit required for efficient T-cell activation consisted of two ligated TCRs within a distance of 20 nanometers, if TCRs were stably engaged by monovalent antibody fragments. In contrast, antigenic pMHCs stimulated T-cells robustly as well-isolated entities. These results identify the minimal requirements for effective TCR-triggering and validate the exceptional stimulatory potency of transiently engaging pMHCs. ### Competing Interest Statement The authors have declared no competing interest.
Translated title of the contributionDNA origami demonstrate the unique stimulatory power of single pMHCs as T-cell antigens
Original languageEnglish
DOIs
Publication statusPublished - 24 Jun 2020

Keywords

  • biophysics

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