IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms8484.html
   My bibliography  Save this article

Thymoproteasomes produce unique peptide motifs for positive selection of CD8+ T cells

Author

Listed:
  • Katsuhiro Sasaki

    (Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo
    Present address: Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.)

  • Kensuke Takada

    (Institute for Genome Research, University of Tokushima)

  • Yuki Ohte

    (Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo)

  • Hiroyuki Kondo

    (Institute for Genome Research, University of Tokushima)

  • Hiroyuki Sorimachi

    (Calpain Project, Tokyo Metropolitan Institute of Medical Science)

  • Keiji Tanaka

    (Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science)

  • Yousuke Takahama

    (Institute for Genome Research, University of Tokushima)

  • Shigeo Murata

    (Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo)

Abstract

Positive selection in the thymus provides low-affinity T-cell receptor (TCR) engagement to support the development of potentially useful self-major histocompatibility complex class I (MHC-I)-restricted T cells. Optimal positive selection of CD8+ T cells requires cortical thymic epithelial cells that express β5t-containing thymoproteasomes (tCPs). However, how tCPs govern positive selection is unclear. Here we show that the tCPs produce unique cleavage motifs in digested peptides and in MHC-I-associated peptides. Interestingly, MHC-I-associated peptides carrying these tCP-dependent motifs are enriched with low-affinity TCR ligands that efficiently induce the positive selection of functionally competent CD8+ T cells in antigen-specific TCR-transgenic models. These results suggest that tCPs contribute to the positive selection of CD8+ T cells by preferentially producing low-affinity TCR ligand peptides.

Suggested Citation

  • Katsuhiro Sasaki & Kensuke Takada & Yuki Ohte & Hiroyuki Kondo & Hiroyuki Sorimachi & Keiji Tanaka & Yousuke Takahama & Shigeo Murata, 2015. "Thymoproteasomes produce unique peptide motifs for positive selection of CD8+ T cells," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8484
    DOI: 10.1038/ncomms8484
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms8484
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms8484?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8484. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.