Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding

  1. Paul Chappell
  2. El Kahina Meziane
  3. Michael Harrison
  4. Łukasz Magiera
  5. Clemens Hermann
  6. Laura Mears
  7. Antony G Wrobel
  8. Charlotte Durant
  9. Lise Lotte Nielsen
  10. Soren Buus
  11. Nicola Ternette
  12. William Mwangi
  13. Colin Butter
  14. Venugopal Nair
  15. Trudy Ahyee
  16. Richard Duggleby
  17. Alejandro Madrigal
  18. Pietro Roversi
  19. Susan M Lea
  20. Jim Kaufman  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. University of Cambridge, United Kingdom
  3. University of Copenhagen, Denmark
  4. Pirbright Institute, United Kingdom
  5. The Royal Free Hospital, United Kingdom

Abstract

Highly polymorphic MHC molecules are at the heart of adaptive immune responses, playing crucial roles in many kinds of disease and in vaccination. We report that breadth of peptide presentation and level of cell surface expression of class I molecules are inversely correlated in both chickens and humans. This relationship correlates with protective responses against infectious pathogens including Marek's disease virus leading to lethal tumours in chickens and HIV infection progressing to AIDS in humans. We propose that differences in peptide binding repertoire define two groups of MHC class I molecules strategically evolved as generalists and specialists for different modes of pathogen resistance. We suggest that differences in cell surface expression level ensure the development of optimal peripheral T cell responses. The inverse relationship of peptide repertoire and expression is evidently a fundamental property of MHC molecules, with ramifications extending beyond immunology and medicine to evolutionary biology and conservation.

Article and author information

Author details

  1. Paul Chappell

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. El Kahina Meziane

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Michael Harrison

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Łukasz Magiera

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Clemens Hermann

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Laura Mears

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Antony G Wrobel

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Charlotte Durant

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Lise Lotte Nielsen

    Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  10. Soren Buus

    Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  11. Nicola Ternette

    Target Discovery Institute, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  12. William Mwangi

    Pirbright Institute, Compton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  13. Colin Butter

    Pirbright Institute, Compton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  14. Venugopal Nair

    Pirbright Institute, Compton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  15. Trudy Ahyee

    Anthony Nolan Research Institute, The Royal Free Hospital, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  16. Richard Duggleby

    Anthony Nolan Research Institute, The Royal Free Hospital, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  17. Alejandro Madrigal

    Anthony Nolan Research Institute, The Royal Free Hospital, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  18. Pietro Roversi

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  19. Susan M Lea

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  20. Jim Kaufman

    Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    jfk31@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Arup K Chakraborty, Massachusetts Institute of Technology, United States

Ethics

Animal experimentation: All procedures involving chickens were carried out at the University of Cambridge under Home Office project license PPL 80/2420 and with ethical approval of the Local Ethical Review Committee.

Human subjects: Anthony Nolan registrants signed written consent forms, with all procedures carried out under Human Tissue Act licensing number 22513 and with approval of the local Research Ethics committee (REC).

Version history

  1. Received: October 26, 2014
  2. Accepted: April 10, 2015
  3. Accepted Manuscript published: April 10, 2015 (version 1)
  4. Version of Record published: May 6, 2015 (version 2)

Copyright

© 2015, Chappell 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. Paul Chappell
  2. El Kahina Meziane
  3. Michael Harrison
  4. Łukasz Magiera
  5. Clemens Hermann
  6. Laura Mears
  7. Antony G Wrobel
  8. Charlotte Durant
  9. Lise Lotte Nielsen
  10. Soren Buus
  11. Nicola Ternette
  12. William Mwangi
  13. Colin Butter
  14. Venugopal Nair
  15. Trudy Ahyee
  16. Richard Duggleby
  17. Alejandro Madrigal
  18. Pietro Roversi
  19. Susan M Lea
  20. Jim Kaufman
(2015)
Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding
eLife 4:e05345.
https://doi.org/10.7554/eLife.05345

Share this article

https://doi.org/10.7554/eLife.05345

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