1. Immunology and Inflammation
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Tissue-specific shaping of the TCR repertoire and antigen specificity of iNKT cells

  1. Rebeca Jimeno
  2. Marta Lebrusant-Fernandez
  3. Christian Margreitter
  4. Beth Lucas
  5. Natacha Veerapen
  6. Gurdyal S Besra
  7. Franca Fraternali
  8. Jo Spencer
  9. Graham Anderson
  10. Patricia Barral  Is a corresponding author
  1. King's College London, United Kingdom
  2. University of Birmingham, United Kingdom
Research Article
  • Cited 2
  • Views 1,757
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Cite this article as: eLife 2019;8:e51663 doi: 10.7554/eLife.51663

Abstract

Tissue homeostasis is critically dependent on the function of tissue-resident lymphocytes, including lipid-reactive invariant natural killer T (iNKT) cells. Yet, if and how the tissue environment shapes the antigen specificity of iNKT cells remains unknown. By analysing iNKT cells from lymphoid tissues of mice and humans we demonstrate that their T cell receptor (TCR) repertoire is highly diverse and is distinct for cells from various tissues resulting in differential lipid-antigen recognition. Within peripheral tissues iNKT cell recent thymic emigrants exhibit a different TCR repertoire than mature cells, suggesting that the iNKT population is shaped after arrival to the periphery. Consistent with this, iNKT cells from different organs show distinct basal activation, proliferation and clonal expansion. Moreover, the iNKT cell TCR repertoire changes following immunisation and is shaped by age and environmental changes. Thus, post-thymic modification of the TCR-repertoire underpins the distinct antigen specificity for iNKT cells in peripheral tissues.

Article and author information

Author details

  1. Rebeca Jimeno

    The Peter Gorer Department of Immunobiology, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  2. Marta Lebrusant-Fernandez

    The Peter Gorer Department of Immunobiology, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  3. Christian Margreitter

    Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  4. Beth Lucas

    Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  5. Natacha Veerapen

    Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  6. Gurdyal S Besra

    Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  7. Franca Fraternali

    Randall Division of Cell and Molecular Biophysics, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3143-6574

  8. Jo Spencer

    The Peter Gorer Department of Immunobiology, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  9. Graham Anderson

    Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

  10. Patricia Barral

    The Peter Gorer Department of Immunobiology, King's College London, London, United Kingdom
    For correspondence
    patricia.barral@kcl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4324-8973

Funding

Medical Research Council (MR/L008157/1)

  • Patricia Barral

Marie Curie Intraeuropean Fellowship (H2020-MSCA-IF-2015-703639)

  • Rebeca Jimeno

Medical Research Council (DKAA.RRAK18742)

  • Graham Anderson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal experiments were approved by the Francis Crick Institute's and the King's College London's Animal Welfare and Ethical Review Body and the United Kingdom Home Office.

Human subjects: Human tissues used in this study were collected with ethical approval from UK Research Ethics Committees administered through the Integrated Research Application System. All samples were collected with informed consent.

Reviewing Editor

  1. Chyung-Ru Wang, Northwestern University, United States

Publication history

  1. Received: September 5, 2019
  2. Accepted: December 15, 2019
  3. Accepted Manuscript published: December 16, 2019 (version 1)
  4. Version of Record published: December 24, 2019 (version 2)
  5. Version of Record updated: March 18, 2020 (version 3)

Copyright

© 2019, Jimeno et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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