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

Constraining CD45 exclusion at close-contacts provides a mechanism for discriminatory T-cell receptor signalling

View ORCID ProfileRicardo A Fernandes, Kristina A Ganzinger, Justin Tzou, Peter Jonsson, Steven F Lee, Matthieu Palayret, Ana Mafalda Santos, Veronica T Chang, Charlotte Macleod, B Christoffer Lagerholm, Alan E Lindsay, Omer Dushek, Andreas Tilevik, Simon J Davis, David Klenerman
doi: https://doi.org/10.1101/109785
Ricardo A Fernandes
Stanford University;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ricardo A Fernandes
Kristina A Ganzinger
Max-Planck-Institut fur Biochemie;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Justin Tzou
University of Notre Dame;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter Jonsson
Lund University;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Steven F Lee
University of Cambridge;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthieu Palayret
University of Cambridge;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ana Mafalda Santos
University of Oxford;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Veronica T Chang
University of Oxford;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Charlotte Macleod
University of Cambridge;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
B Christoffer Lagerholm
University of Oxford;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alan E Lindsay
University of Notre Dame;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Omer Dushek
University of Oxford;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andreas Tilevik
University of Skovde
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simon J Davis
University of Oxford;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Klenerman
University of Cambridge;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: dk10012@cam.ac.uk
  • Abstract
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

The T-cell receptor (TCR) must discriminate between peptides bound to major histocompatibility complex proteins and yet it can be triggered even without ligands at close contacts characterized by local depletion of the phosphatase, CD45. Here, we use a quantitative treatment of signaling that incorporates moving-boundary passage time calculations and is reliant only upon receptor dwell-time at close contacts to reconcile the contradictory properties of TCR triggering. We validate the model by showing that signaling is inversely related to close contact growth-rate and sensitive to the local balance of kinase and phosphatase activities. The model predicts that the small size of close contacts imposed by cell topography, and their short duration owing to the destabilizing effects of, for example, the glycocalyx, crucially underpins ligand discrimination by T cells without recourse to classical proofreading schemes. Based on simple physical principles, therefore, our model accounts for the main features of TCR triggering.

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 February 19, 2017.
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.
Constraining CD45 exclusion at close-contacts provides a mechanism for discriminatory T-cell receptor signalling
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
Constraining CD45 exclusion at close-contacts provides a mechanism for discriminatory T-cell receptor signalling
Ricardo A Fernandes, Kristina A Ganzinger, Justin Tzou, Peter Jonsson, Steven F Lee, Matthieu Palayret, Ana Mafalda Santos, Veronica T Chang, Charlotte Macleod, B Christoffer Lagerholm, Alan E Lindsay, Omer Dushek, Andreas Tilevik, Simon J Davis, David Klenerman
bioRxiv 109785; doi: https://doi.org/10.1101/109785
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Constraining CD45 exclusion at close-contacts provides a mechanism for discriminatory T-cell receptor signalling
Ricardo A Fernandes, Kristina A Ganzinger, Justin Tzou, Peter Jonsson, Steven F Lee, Matthieu Palayret, Ana Mafalda Santos, Veronica T Chang, Charlotte Macleod, B Christoffer Lagerholm, Alan E Lindsay, Omer Dushek, Andreas Tilevik, Simon J Davis, David Klenerman
bioRxiv 109785; doi: https://doi.org/10.1101/109785

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

  • Immunology
Subject Areas
All Articles
  • Animal Behavior and Cognition (996)
  • Biochemistry (1485)
  • Bioengineering (938)
  • Bioinformatics (6803)
  • Biophysics (2414)
  • Cancer Biology (1782)
  • Cell Biology (2514)
  • Clinical Trials (106)
  • Developmental Biology (1683)
  • Ecology (2553)
  • Epidemiology (1488)
  • Evolutionary Biology (5003)
  • Genetics (3598)
  • Genomics (4614)
  • Immunology (1157)
  • Microbiology (4222)
  • Molecular Biology (1617)
  • Neuroscience (10743)
  • Paleontology (81)
  • Pathology (236)
  • Pharmacology and Toxicology (407)
  • Physiology (552)
  • Plant Biology (1445)
  • Scientific Communication and Education (410)
  • Synthetic Biology (542)
  • Systems Biology (1868)
  • Zoology (257)