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

TCR affinity controls the dynamics but not the functional specification of the Th1 response to mycobacteria

View ORCID ProfileNayan D Bhattacharyya, View ORCID ProfileClaudio Counoupas, Lina Daniel, View ORCID ProfileGuoliang Zhang, Stuart J Cook, Taylor A Cootes, View ORCID ProfileSebastian A Stifter, David G Bowen, James A Triccas, View ORCID ProfilePatrick Bertolino, View ORCID ProfileWarwick J Britton, View ORCID ProfileCarl G Feng
doi: https://doi.org/10.1101/2020.10.25.353763
Nayan D Bhattacharyya
1Immunology and Host Defense Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine & Health, The University of Sydney, NSW, 2006, Australia
2Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Nayan D Bhattacharyya
Claudio Counoupas
3Microbial Pathogenesis and Immunity Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine & Health, University of Sydney, NSW, 2006, Australia
2Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Claudio Counoupas
Lina Daniel
1Immunology and Host Defense Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine & Health, The University of Sydney, NSW, 2006, Australia
2Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Guoliang Zhang
4National Clinical Research Center for Infectious Diseases, Guangdong Key Laboratory of Emerging Infectious Diseases, Shenzhen Third People’s Hospital, Southern University of Science and Technology, Shenzhen, China
1Immunology and Host Defense Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine & Health, The University of Sydney, NSW, 2006, Australia
2Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Guoliang Zhang
Stuart J Cook
5Immune Imaging Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Taylor A Cootes
1Immunology and Host Defense Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine & Health, The University of Sydney, NSW, 2006, Australia
2Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sebastian A Stifter
1Immunology and Host Defense Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine & Health, The University of Sydney, NSW, 2006, Australia
2Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Sebastian A Stifter
David G Bowen
7Liver Immunology Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia
8AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James A Triccas
3Microbial Pathogenesis and Immunity Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine & Health, University of Sydney, NSW, 2006, Australia
2Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia
6Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, NSW, 2006, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patrick Bertolino
7Liver Immunology Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia
8AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Patrick Bertolino
Warwick J Britton
2Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Warwick J Britton
Carl G Feng
1Immunology and Host Defense Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine & Health, The University of Sydney, NSW, 2006, Australia
2Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW, 2050, Australia
6Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, NSW, 2006, Australia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Carl G Feng
  • For correspondence: carl.feng@sydney.edu.au
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The quality of T cell responses depends on the lymphocytes’ ability to undergo clonal expansion, acquire effector functions and traffic to the site of infection. Although TCR signal strength is thought to dominantly shape the T cell response, by using TCR transgenic CD4+ T cells with different pMHC binding affinity, we reveal that TCR affinity does not control Th1 effector function acquisition nor the functional output of individual effectors following mycobacterial infection. Rather, TCR affinity calibrates the rate of cell division to synchronize the distinct processes of T cell proliferation, differentiation and trafficking. By timing cell division-dependent IL-12R expression, TCR affinity controls when T cells become receptive to Th1-imprinting IL-12 signals, determining the emergence and magnitude of the Th1 effector pool. These findings reveal a distinct yet cooperative role for IL-12 and TCR signalling in Th1 differentiation and suggests that the temporal activation of clones with different TCR affinity is a major strategy to coordinate immune surveillance against persistent pathogens.

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 October 26, 2020.
Download PDF
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.
TCR affinity controls the dynamics but not the functional specification of the Th1 response to mycobacteria
(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
TCR affinity controls the dynamics but not the functional specification of the Th1 response to mycobacteria
Nayan D Bhattacharyya, Claudio Counoupas, Lina Daniel, Guoliang Zhang, Stuart J Cook, Taylor A Cootes, Sebastian A Stifter, David G Bowen, James A Triccas, Patrick Bertolino, Warwick J Britton, Carl G Feng
bioRxiv 2020.10.25.353763; doi: https://doi.org/10.1101/2020.10.25.353763
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
TCR affinity controls the dynamics but not the functional specification of the Th1 response to mycobacteria
Nayan D Bhattacharyya, Claudio Counoupas, Lina Daniel, Guoliang Zhang, Stuart J Cook, Taylor A Cootes, Sebastian A Stifter, David G Bowen, James A Triccas, Patrick Bertolino, Warwick J Britton, Carl G Feng
bioRxiv 2020.10.25.353763; doi: https://doi.org/10.1101/2020.10.25.353763

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 (2513)
  • Biochemistry (4957)
  • Bioengineering (3456)
  • Bioinformatics (15148)
  • Biophysics (6868)
  • Cancer Biology (5365)
  • Cell Biology (7692)
  • Clinical Trials (138)
  • Developmental Biology (4509)
  • Ecology (7117)
  • Epidemiology (2059)
  • Evolutionary Biology (10193)
  • Genetics (7494)
  • Genomics (9758)
  • Immunology (4808)
  • Microbiology (13153)
  • Molecular Biology (5114)
  • Neuroscience (29321)
  • Paleontology (203)
  • Pathology (833)
  • Pharmacology and Toxicology (1458)
  • Physiology (2123)
  • Plant Biology (4723)
  • Scientific Communication and Education (1004)
  • Synthetic Biology (1336)
  • Systems Biology (3997)
  • Zoology (768)