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DOI10.1073/pnas.2016857118
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.; Schneider M.C.; Kurz E.; Bamieh V.; Brameshuber M.; Preiner J.; Jungmann R.; Stockinger H.; Schütz G.J.; Huppa J.B.; Sevcsik E.
发表日期2021
ISSN00278424
卷号118期号:4
英文摘要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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词DNA origami; Nanobiotechnology; PMHC; Serial engagement; T cell activation
语种英语
scopus关键词DNA; T lymphocyte antigen; T lymphocyte receptor; animal experiment; animal tissue; antibody detection; Article; cell activation; cell communication; controlled study; mouse; nanobiotechnology; nonhuman; priority journal; T lymphocyte activation
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180853
作者单位Institute of Applied Physics, TU Wien, Vienna, 1040, Austria; Center for Pathophysiology, Infectiology and Immunology, Institute for Hygiene and Applied Immunology, Medical University of Vienna, Vienna, 1090, Austria; Max Planck Institute of Biochemistry, Martinsried, 82152, Germany; Faculty of Physics, Center for Nanoscience, Ludwig Maximilian University, Munich, 80539, Germany; University of Applied Sciences Upper Austria, Linz, 4020, Austria; Kennedy Institute of Rheumatology, University of Oxford, Oxford, OX3 7FY, United Kingdom
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Hellmeier J.,Platzer R.,Eklund A.S.,et al. DNA origami demonstrate the unique stimulatory power of single pMHCs as T cell antigens[J],2021,118(4).
APA Hellmeier J..,Platzer R..,Eklund A.S..,Schlichthaerle T..,Karner A..,...&Sevcsik E..(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).
MLA Hellmeier J.,et al."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(2021).
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