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

Hellmeier, Joschka; Platzer, Rene; Eklund, Alexandra S.; Schlichthaerle, Thomas; Karner, Andreas; Motsch, Viktoria; Schneider, Magdalena C.; Kurz, Elke; Bamieh, Victor; Brameshuber, Mario; Preiner, Johannes; Jungmann, Ralf; Stockinger, Hannes; Schutz, Gerhard J.; Huppa, Johannes B. und Sevcsik, Eva (2021): DNA origami demonstrate the unique stimulatory power of single pMHCs as T cell antigens. In: Proceedings of the National Academy of Sciences of the United States of America, Bd. 118, Nr. 4, e2016857118

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 (APC5). 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 TCR5 via stably binding monovalent antibody fragments, we found the minimum signaling unit promoting efficient T cell activation to consist of two antibody-ligated TCR5 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 TCR5 as minimal receptor entities for effective TCR triggering yet validate the exceptional stimulatory potency of single isolated pMHC molecules.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Physik
• Themengebiete: 500 Naturwissenschaften und Mathematik > 530 Physik
• ISSN: 0027-8424
• Sprache: Englisch