IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms6369.html
   My bibliography  Save this article

Divergent paths for the selection of immunodominant epitopes from distinct antigenic sources

Author

Listed:
  • AeRyon Kim

    (Johns Hopkins University School of Medicine)

  • Isamu Z. Hartman

    (The Graduate Program in Immunology, Johns Hopkins University School of Medicine
    Present address: Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA)

  • Brad Poore

    (Johns Hopkins University School of Medicine)

  • Tatiana Boronina

    (Mass Spectrometry and Proteomics Facility, The Johns Hopkins University School of Medicine)

  • Robert N. Cole

    (Mass Spectrometry and Proteomics Facility, The Johns Hopkins University School of Medicine)

  • Nianbin Song

    (The Graduate Program in Immunology, Johns Hopkins University School of Medicine)

  • M. Teresa Ciudad

    (Physiology and Immunology, Laboratori d'Immunologia Cellular, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona)

  • Rachel R. Caspi

    (Laboratory of Immunology, National Eye Institute, NIH)

  • Dolores Jaraquemada

    (Physiology and Immunology, Laboratori d'Immunologia Cellular, Institut de Biotecnologia i Biomedicina, Universitat Autònoma de Barcelona)

  • Scheherazade Sadegh-Nasseri

    (Johns Hopkins University School of Medicine
    The Graduate Program in Immunology, Johns Hopkins University School of Medicine)

Abstract

Immunodominant epitopes are few selected epitopes from complex antigens that initiate T-cell responses. Here to provide further insights into this process, we use a reductionist cell-free antigen-processing system composed of defined components. We use the system to characterize steps in antigen processing of pathogen-derived proteins or autoantigens and we find distinct paths for peptide processing and selection. Autoantigen-derived immunodominant epitopes are resistant to digestion by cathepsins, whereas pathogen-derived epitopes are sensitive. Sensitivity to cathepsins enforces capture of pathogen-derived epitopes by major histocompatibility complex class II (MHC class II) before processing, and resistance to HLA-DM-mediated-dissociation preserves the longevity of those epitopes. We show that immunodominance is established by higher relative abundance of the selected epitopes, which survive cathepsin digestion either by binding to MHC class II and resisting DM-mediated-dissociation, or being chemically resistant to cathepsins degradation. Non-dominant epitopes are sensitive to both DM and cathepsins and are destroyed.

Suggested Citation

  • AeRyon Kim & Isamu Z. Hartman & Brad Poore & Tatiana Boronina & Robert N. Cole & Nianbin Song & M. Teresa Ciudad & Rachel R. Caspi & Dolores Jaraquemada & Scheherazade Sadegh-Nasseri, 2014. "Divergent paths for the selection of immunodominant epitopes from distinct antigenic sources," Nature Communications, Nature, vol. 5(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6369
    DOI: 10.1038/ncomms6369
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms6369
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms6369?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Ashley M. Curran & Alexander A. Girgis & Yura Jang & Jonathan D. Crawford & Mekha A. Thomas & Ryan Kawalerski & Jeff Coller & Clifton O. Bingham & Chan Hyun Na & Erika Darrah, 2023. "Citrullination modulates antigen processing and presentation by revealing cryptic epitopes in rheumatoid arthritis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    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:5:y:2014:i:1:d:10.1038_ncomms6369. 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.