IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms11112.html
   My bibliography  Save this article

Individual heritable differences result in unique cell lymphocyte receptor repertoires of naïve and antigen-experienced cells

Author

Listed:
  • Florian Rubelt

    (Stanford University School of Medicine)

  • Christopher R. Bolen

    (Stanford University School of Medicine
    Present address: Genentech, Inc., 1 DNA Way, MS 93, South San Francisco, California 94080, USA)

  • Helen M. McGuire

    (Stanford University School of Medicine
    Present address: T Cell Biology Laboratory, Centenary Institute of Cancer Medicine and Cell Biology, Camperdown, New South Wales, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia)

  • Jason A. Vander Heiden

    (Deaptment of Computational Biology & Bioinformatics, Yale University)

  • Daniel Gadala-Maria

    (Deaptment of Computational Biology & Bioinformatics, Yale University)

  • Mikhail Levin

    (University of Texas Southwestern Medical Center)

  • Ghia M. Euskirchen

    (Stanford University School of Medicine)

  • Murad R. Mamedov

    (Program in Immunology, Stanford University)

  • Gary E. Swan

    (Stanford Prevention Research Center, Stanford University School of Medicine)

  • Cornelia L. Dekker

    (Stanford University School of Medicine)

  • Lindsay G. Cowell

    (University of Texas Southwestern Medical Center)

  • Steven H. Kleinstein

    (Deaptment of Computational Biology & Bioinformatics, Yale University
    Yale University School of Medicine
    Yale University School of Medicine)

  • Mark M. Davis

    (Stanford University School of Medicine
    Howard Hughes Medical Institute, Stanford University School of Medicine
    Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine)

Abstract

The adaptive immune system’s capability to protect the body requires a highly diverse lymphocyte antigen receptor repertoire. However, the influence of individual genetic and epigenetic differences on these repertoires is not typically measured. By leveraging the unique characteristics of B, CD4+ T and CD8+ T-lymphocyte subsets from monozygotic twins, we quantify the impact of heritable factors on both the V(D)J recombination process and on thymic selection. We show that the resulting biases in both V(D)J usage and N/P addition lengths, which are found in naïve and antigen experienced cells, contribute to significant variation in the CDR3 region. Moreover, we show that the relative usage of V and J gene segments is chromosomally biased, with ∼1.5 times as many rearrangements originating from a single chromosome. These data refine our understanding of the heritable mechanisms affecting the repertoire, and show that biases are evident on a chromosome-wide level.

Suggested Citation

  • Florian Rubelt & Christopher R. Bolen & Helen M. McGuire & Jason A. Vander Heiden & Daniel Gadala-Maria & Mikhail Levin & Ghia M. Euskirchen & Murad R. Mamedov & Gary E. Swan & Cornelia L. Dekker & Li, 2016. "Individual heritable differences result in unique cell lymphocyte receptor repertoires of naïve and antigen-experienced cells," Nature Communications, Nature, vol. 7(1), pages 1-12, June.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11112
    DOI: 10.1038/ncomms11112
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms11112
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms11112?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. Oscar L. Rodriguez & Yana Safonova & Catherine A. Silver & Kaitlyn Shields & William S. Gibson & Justin T. Kos & David Tieri & Hanzhong Ke & Katherine J. L. Jackson & Scott D. Boyd & Melissa L. Smith , 2023. "Genetic variation in the immunoglobulin heavy chain locus shapes the human antibody repertoire," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Sonwabile Dzanibe & Aaron J. Wilk & Susan Canny & Thanmayi Ranganath & Berenice Alinde & Florian Rubelt & Huang Huang & Mark M. Davis & Susan P. Holmes & Heather B. Jaspan & Catherine A. Blish & Clive, 2024. "Premature skewing of T cell receptor clonality and delayed memory expansion in HIV-exposed infants," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Jani Huuhtanen & Liang Chen & Emmi Jokinen & Henna Kasanen & Tapio Lönnberg & Anna Kreutzman & Katriina Peltola & Micaela Hernberg & Chunlin Wang & Cassian Yee & Harri Lähdesmäki & Mark M. Davis & Sat, 2022. "Evolution and modulation of antigen-specific T cell responses in melanoma patients," Nature Communications, Nature, vol. 13(1), pages 1-14, 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:7:y:2016:i:1:d:10.1038_ncomms11112. 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.