1. Immunology and Inflammation
  2. Microbiology and Infectious Disease
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Toxoplasma gondii peptide ligands open the gate of the HLA class I binding groove

  1. Curtis McMurtrey
  2. Thomas Trolle
  3. Tiffany Sansom
  4. Soumya G Remesh
  5. Thomas Kaever
  6. Wilfried Bardet
  7. Kenneth Jackson
  8. Morten Nielsen
  9. Rima McLeod
  10. Dirk M Zajonc
  11. Ira J Blader
  12. Bjoern Peters
  13. Alessandro Sette
  14. William Hildebrand  Is a corresponding author
  1. University of Oklahoma Health Sciences Center, United States
  2. Technical University of Denmark, Denmark
  3. University at Buffalo School of Medicine, United States
  4. La Jolla Institute for Allergy and Immunology, United States
  5. University of Chicago, United States
  6. University of Oklahoma Health Science Center, United States
Research Article
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Cite this article as: eLife 2016;5:e12556 doi: 10.7554/eLife.12556

Abstract

HLA class I presentation of pathogen-derived peptide ligands is essential for CD8+ T-cell recognition of Toxoplasma gondii infected cells. Currently, little data exist pertaining to peptides that are presented after T. gondii infection. Herein we purify HLA-A*02:01 complexes from T. gondii infected cells and characterize the peptide ligands using LCMS. We identify 195 T. gondii encoded ligands originating from both secreted and cytoplasmic proteins. Surprisingly, T. gondii ligands are significantly longer than uninfected host ligands, and these longer pathogen-derived peptides maintain a canonical N-terminal binding core yet exhibit a C-terminal extension of 1-30 amino acids. Structural analysis demonstrates that binding of extended peptides opens the HLA class I F' pocket, allowing the C-terminal extension to protrude through one end of the binding groove. In summary, we demonstrate that unrealized structural flexibility makes MHC class I receptive to parasite-derived ligands that exhibit unique C-terminal peptide extensions.

Article and author information

Author details

  1. Curtis McMurtrey

    Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Thomas Trolle

    Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  3. Tiffany Sansom

    Department of Microbiology and Immunology, University at Buffalo School of Medicine, Buffalo, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Soumya G Remesh

    La Jolla Institute for Allergy and Immunology, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Thomas Kaever

    La Jolla Institute for Allergy and Immunology, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Wilfried Bardet

    Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Kenneth Jackson

    Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Morten Nielsen

    Center for Biological Sequence Analysis, Technical University of Denmark, Kongens Lyngby, Denmark
    Competing interests
    The authors declare that no competing interests exist.
  9. Rima McLeod

    University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Dirk M Zajonc

    La Jolla Institute for Allergy and Immunology, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Ira J Blader

    Department of Microbiology and Immunology, University at Buffalo School of Medicine, Buffalo, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Bjoern Peters

    La Jolla Institute for Allergy and Immunology, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Alessandro Sette

    La Jolla Institute for Allergy and Immunology, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. William Hildebrand

    Department of Microbiology and Immunology, University of Oklahoma Health Science Center, Oklahoma City, United States
    For correspondence
    william-hildebrand@ouhsc.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Michael S Gilmore, Harvard Medical School, United States

Publication history

  1. Received: October 26, 2015
  2. Accepted: January 28, 2016
  3. Accepted Manuscript published: January 29, 2016 (version 1)
  4. Version of Record published: February 23, 2016 (version 2)

Copyright

© 2016, McMurtrey 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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