TAPBPR alters MHC class I peptide presentation by functioning as a peptide exchange catalyst

  1. Clemens Hermann
  2. Andy van Hateren
  3. Nico Trautwein
  4. Andreas Neerincx
  5. Patrick J Duriez
  6. Stefan Stevanović
  7. John Trowsdale
  8. Janet E Deane
  9. Tim Elliott
  10. Louise H Boyle  Is a corresponding author
  1. University of Cape Town, South Africa
  2. University of Southampton, United Kingdom
  3. Eberhard Karls University Tübingen, Germany
  4. University of Cambridge, United Kingdom

Abstract

Our understanding of the antigen presentation pathway has recently been enhanced with the identification that the tapasin-related protein TAPBPR is a second MHC I-specific chaperone. We sought to determine whether, like tapasin, TAPBPR can also influence MHC I peptide selection by functioning as a peptide exchange catalyst. We show that TAPBPR can catalyse the dissociation of peptides from peptide-MHC I complexes, enhance the loading of peptide-receptive MHC I molecules, and discriminate between peptides based on affinity in vitro. In cells, the depletion of TAPBPR increased the diversity of peptides presented on MHC I molecules, suggesting that TAPBPR is involved in restricting peptide presentation. Our results suggest TAPBPR binds to MHC I in a peptide-receptive state and, like tapasin, works to enhance peptide optimisation. It is now clear there are two MHC class I specific peptide editors, tapasin and TAPBPR, intimately involved in controlling peptide presentation to the immune system.

Article and author information

Author details

  1. Clemens Hermann

    Department of Integrated Biomedical Sciences, Division of Chemical and 20 Systems Biology, Institute for Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  2. Andy van Hateren

    Faculty of Medicine and Institute for Life Science, University of Southampton, Southampton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Nico Trautwein

    Department of Immunology, Eberhard Karls University Tübingen, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Andreas Neerincx

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Patrick J Duriez

    Cancer Research UK Protein Core Facility, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Stefan Stevanović

    Department of Immunology, Eberhard Karls University Tübingen, Tübingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. John Trowsdale

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Janet E Deane

    Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Tim Elliott

    Faculty of Medicine and Institute for Life Science, University of Southampton, Southampton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Louise H Boyle

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    lhb22@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Diane Mathis, Harvard Medical School, United States

Publication history

  1. Received: June 22, 2015
  2. Accepted: October 5, 2015
  3. Accepted Manuscript published: October 6, 2015 (version 1)
  4. Version of Record published: January 11, 2016 (version 2)

Copyright

© 2015, Hermann 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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  1. Clemens Hermann
  2. Andy van Hateren
  3. Nico Trautwein
  4. Andreas Neerincx
  5. Patrick J Duriez
  6. Stefan Stevanović
  7. John Trowsdale
  8. Janet E Deane
  9. Tim Elliott
  10. Louise H Boyle
(2015)
TAPBPR alters MHC class I peptide presentation by functioning as a peptide exchange catalyst
eLife 4:e09617.
https://doi.org/10.7554/eLife.09617

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