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

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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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