@article{2743175e7bbd46fd9d1f80bbb70fa9b1,
title = "DNA origami demonstrate the unique stimulatory power of single pMHCs as T cell antigens",
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, PMHC, Serial engagement, T cell activation",
author = "Joschka Hellmeier and Rene Platzer and Eklund, {Alexandra S.} and Thomas Schlichthaerle and Andreas Karner and Viktoria Motsch and Schneider, {Magdalena C.} and Elke Kurz and Victor Bamieh and Mario Brameshuber and Johannes Preiner and Ralf Jungmann and Hannes Stockinger and Sch{\"u}tz, {Gerhard J.} and Huppa, {Johannes B.} and Eva Sevcsik",
note = "Funding Information: ACKNOWLEDGMENTS. This work was supported by the Austrian Science Fund (FWF projects V538-B26 [E.S. and J.B.H.] and I4662-B [M.B.]; the PhD program Cell Communication in Health and Disease W1205, R.P., J.B.H. and H.S.), the TU Wien doctoral college BioInterface (J.B.H.), the European Fund for Regional Development (EFRE, IWB2020, A.K. and J.P.), the Federal State of Upper Austria (J.P.), the Vienna Science and Technology Fund (WWTF, LS13-030, G.J.S. and J.B.H.), the Boehringer Ingelheim Fonds (R.P.), the German Research Foundation through the Emmy Noether Program (DFG JU 2957/1-1, R.J.), the SFB1032 (project A11, R.J.), the European Research Council through an ERC Starting Grant (MolMap; grant agreement number 680241, R.J.), the Allen Distinguished Investigator Program through The Paul G. Allen Frontiers Group (R.J.), the Danish National Research Foundation (Centre for Cellular Signal Patterns, DNRF135, R.J.), the Human Frontier Science Program through a Young Investigator Grant (HFSP RGY0065), the Funding Information: Munich graduate school (T.S.), and the Wellcome Trust (Principal Research Fellowship 100262 Z/12/Z, E.K.). We thank V. M{\"u}hlgrabner for help with tissue culture. Publisher Copyright: {\textcopyright} 2021 National Academy of Sciences. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = jan,
day = "26",
doi = "10.1073/pnas.2016857118",
language = "English",
volume = "118",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "4",
}