Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

DNA origami patterning of synthetic T cell receptors reveals spatial control of the sensitivity and kinetics of signal activation

View ORCID ProfileRui Dong, View ORCID ProfileTural Aksel, View ORCID ProfileWaipan Chan, View ORCID ProfileRonald N. Germain, View ORCID ProfileRonald D. Vale, View ORCID ProfileShawn M. Douglas
doi: https://doi.org/10.1101/2021.03.12.434905
Rui Dong
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rui Dong
Tural Aksel
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tural Aksel
Waipan Chan
2Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Waipan Chan
Ronald N. Germain
2Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ronald N. Germain
Ronald D. Vale
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA
3The Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ronald D. Vale
  • For correspondence: shawn.douglas@ucsf.edu valer@janelia.hhmi.org
Shawn M. Douglas
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Shawn M. Douglas
  • For correspondence: shawn.douglas@ucsf.edu valer@janelia.hhmi.org
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

SUMMARY

T cell receptor clustering plays a key role in triggering cell activation, but the relationship between the spatial configuration of clusters and elicitation of downstream intracellular signals remains poorly understood. We developed a DNA-origami-based system that is easily adaptable to other cellular systems and enables rich interrogation of responses to a variety of spatially defined inputs. Using a chimeric antigen receptor (CAR) T cell model system with relevance to cancer therapy, we studied signaling dynamics at single cell resolution. We found that the spatial arrangement of receptors determines the ligand density threshold for triggering and encodes the temporal kinetics of signaling activities. We also showed that signaling sensitivity of a small cluster of high-affinity ligands is enhanced when surrounded by non-stimulating low-affinity ligands. Our results suggest that cells measure spatial arrangements of ligands and translates that information into distinct signaling dynamics, and provide insights into engineering new immunotherapies.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted March 13, 2021.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
DNA origami patterning of synthetic T cell receptors reveals spatial control of the sensitivity and kinetics of signal activation
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
DNA origami patterning of synthetic T cell receptors reveals spatial control of the sensitivity and kinetics of signal activation
Rui Dong, Tural Aksel, Waipan Chan, Ronald N. Germain, Ronald D. Vale, Shawn M. Douglas
bioRxiv 2021.03.12.434905; doi: https://doi.org/10.1101/2021.03.12.434905
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
DNA origami patterning of synthetic T cell receptors reveals spatial control of the sensitivity and kinetics of signal activation
Rui Dong, Tural Aksel, Waipan Chan, Ronald N. Germain, Ronald D. Vale, Shawn M. Douglas
bioRxiv 2021.03.12.434905; doi: https://doi.org/10.1101/2021.03.12.434905

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4864)
  • Biochemistry (10821)
  • Bioengineering (8061)
  • Bioinformatics (27369)
  • Biophysics (14014)
  • Cancer Biology (11157)
  • Cell Biology (16094)
  • Clinical Trials (138)
  • Developmental Biology (8806)
  • Ecology (13322)
  • Epidemiology (2067)
  • Evolutionary Biology (17389)
  • Genetics (11704)
  • Genomics (15957)
  • Immunology (11057)
  • Microbiology (26148)
  • Molecular Biology (10674)
  • Neuroscience (56714)
  • Paleontology (422)
  • Pathology (1737)
  • Pharmacology and Toxicology (3012)
  • Physiology (4566)
  • Plant Biology (9662)
  • Scientific Communication and Education (1617)
  • Synthetic Biology (2697)
  • Systems Biology (6993)
  • Zoology (1513)