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

Hellmeier, J., Platzer, R., Eklund, A. S., Schlichthaerle, T., Karner, A., Motsch, V., et al. (2021). DNA origami demonstrate the unique stimulatory power of single pMHCs as T cell antigens. Proceedings of the National Academy of Sciences of the United States of America, 118(4): e2016857118. doi:10.1073/pnas.2016857118.

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 Creators:
Hellmeier, Joschka1, Author
Platzer, Rene1, Author
Eklund, Alexandra S.2, Author              
Schlichthaerle, Thomas2, Author              
Karner, Andreas1, Author
Motsch, Viktoria1, Author
Schneider, Magdalena C.1, Author
Kurz, Elke1, Author
Bamieh, Victor1, Author
Brameshuber, Mario1, Author
Preiner, Johannes1, Author
Jungmann, Ralf2, Author              
Stockinger, Hannes1, Author
Schutz, Gerhard J.1, Author
Huppa, Johannes B.1, Author
Sevcsik, Eva1, Author
Affiliations:
1external, ou_persistent22              
2Jungmann, Ralf / Molecular Imaging and Bionanotechnology, Max Planck Institute of Biochemistry, Max Planck Society, ou_2149679              

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Free keywords: SUPERRESOLUTION MICROSCOPY; RECEPTOR MICROCLUSTERS; LIGAND RECOGNITION; PLASMA-MEMBRANE; ACTIVATION; BINDING; KINETICS; THRESHOLDSScience & Technology - Other Topics; DNA origami; nanobiotechnology; T cell activation; pMHC; serial engagement;
 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.

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Language(s): eng - English
 Dates: 2021-01
 Publication Status: Published online
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000612945500035
DOI: 10.1073/pnas.2016857118
PMID: 33468643
 Degree: -

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Project name : MolMap
Grant ID : 680241
Funding program : ERC Starting Grant
Funding organization : European Research Council

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Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : PNAS
  Other : Proceedings of the National Academy of Sciences of the USA
  Abbreviation : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
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Publ. Info: Washington, D.C. : National Academy of Sciences
Pages: - Volume / Issue: 118 (4) Sequence Number: e2016857118 Start / End Page: - Identifier: ISSN: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230