RT Journal Article
SR Electronic
T1 DNA origami demonstrate the unique stimulatory power of single pMHCs as T-cell antigens
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.24.166850
DO 10.1101/2020.06.24.166850
A1 Joschka Hellmeier
A1 Rene Platzer
A1 Alexandra S. Eklund
A1 Thomas Schlichthärle
A1 Andreas Karner
A1 Viktoria Motsch
A1 Elke Kurz
A1 Victor Bamieh
A1 Mario Brameshuber
A1 Johannes Preiner
A1 Ralf Jungmann
A1 Hannes Stockinger
A1 Gerhard J. Schütz
A1 Johannes B. Huppa
A1 Eva Sevcsik
YR 2020
UL http://biorxiv.org/content/early/2020/06/24/2020.06.24.166850.abstract
AB 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 StatementThe authors have declared no competing interest.