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Publications in Scientific Journals:

J. Hellmeier, R. Platzer, A. Eklund, T. Schlichthaerle, A. Karner, V. Motsch, M. Schneider, E. Kurz, V. Bamieh, M. Brameshuber, J. Preiner, R. Jungmann, H. Stockinger, G. Schütz, J. Huppa, E. Sevcsik:
"DNA origami demonstrate the unique stimulatory power of single pMHCs as T cell antigens";
PNAS - Proceedings of the National Academy of Sciences of the United States of America, 118 (2021), 4; 1 - 11.



English 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 pro- moting 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 enti- ties. These results identify pairs of antibody-bound TCRs as minimal receptor entities for effective TCR triggering yet validate the excep- tional stimulatory potency of single isolated pMHC molecules.


"Official" electronic version of the publication (accessed through its Digital Object Identifier - DOI)
http://dx.doi.org/10.1073/pnas.2016857118

Electronic version of the publication:
https://publik.tuwien.ac.at/files/publik_295212.pdf


Created from the Publication Database of the Vienna University of Technology.