1. Immunology and Inflammation
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Functionally diverse human T cells recognize non-microbial antigens presented by MR1

  1. Marco Lepore
  2. Artem Kalinichenko
  3. Salvatore Calogero
  4. Pavanish Kumar
  5. Bhairav Paleja
  6. Mathias Schmaler
  7. Vipin Narang
  8. Francesca Zolezzi
  9. Michael Poidinger
  10. Lucia Mori
  11. Gennaro De Libero  Is a corresponding author
  1. University of Basel, Switzerland
  2. A*STAR, Singapore
  3. University Hospital Basel, Switzerland
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Cite this article as: eLife 2017;6:e24476 doi: 10.7554/eLife.24476

Abstract

MHC class I-related molecule MR1 presents riboflavin- and folate-related metabolites to mucosal-associated invariant T cells, but it is unknown whether MR1 can present alternative antigens to other T cell lineages. In healthy individuals we identified MR1-restricted T cells (named MR1T cells) displaying diverse TCRs and reacting to MR1-expressing cells in the absence of microbial ligands. Analysis of MR1T cell clones revealed specificity for distinct cell-derived antigens and alternative transcriptional strategies for metabolic programming, cell cycle control and functional polarization following antigen stimulation. Phenotypical and functional characterization of MR1T cell clones showed multiple chemokine receptor expression profiles and secretion of diverse effector molecules, suggesting functional heterogeneity. Accordingly, MR1T cells exhibited distinct T helper-like capacities upon MR1-dependent recognition of target cells expressing physiological levels of surface MR1. These data extend the role of MR1 beyond microbial antigen presentation and indicate MR1T cells are a normal part of the human T cell repertoire.

Article and author information

Author details

  1. Marco Lepore

    Department of Biomedicine,, University of Basel, 4031 Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1353-8224
  2. Artem Kalinichenko

    Department of Biomedicine, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Salvatore Calogero

    Department of Biomedicine, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Pavanish Kumar

    Singapore Immunology Network, A*STAR, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  5. Bhairav Paleja

    Singapore Immunology Network, A*STAR, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  6. Mathias Schmaler

    Department of Biomedicine, University of Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  7. Vipin Narang

    Singapore Immunology Network, A*STAR, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  8. Francesca Zolezzi

    Singapore Immunology Network, A*STAR, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  9. Michael Poidinger

    Singapore Immunology Network, A*STAR, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  10. Lucia Mori

    Departement Biomedicine, University Hospital Basel, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5522-4648
  11. Gennaro De Libero

    Department of Biomedicine, University of Basel, Basel, Switzerland
    For correspondence
    gennaro.delibero@unibas.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0853-7868

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030-149571)

  • Gennaro De Libero

European Commission (643381)

  • Gennaro De Libero

Science and Engineering Research Council (1121480006)

  • Gennaro De Libero

Universität Basel (Core Funding)

  • Gennaro De Libero

Agency for Science, Technology and Research (1201826277)

  • Gennaro De Libero

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

Ethics

Human subjects: Venous blood was taken from healthy donors after informed consent obtained at the time of blood collection under approval of the "Ethikkommision Nordwest und Zentralschweiz/EKNZ (139/13).

Reviewing Editor

  1. Wayne M Yokoyama, Howard Hughes Medical Institute, Washington University School of Medicine, United States

Publication history

  1. Received: December 21, 2016
  2. Accepted: May 17, 2017
  3. Accepted Manuscript published: May 18, 2017 (version 1)
  4. Version of Record published: June 5, 2017 (version 2)
  5. Version of Record updated: June 20, 2017 (version 3)

Copyright

© 2017, Lepore 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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