1. Immunology and Inflammation
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The somatically generated portion of the T cell receptor CDR3α contributes to the MHC allele specificity of the T cell receptor

  1. Philippa Marrack  Is a corresponding author
  2. Sai Harsha Krovi
  3. Daniel Silberman
  4. Janice White
  5. Eleanor Kushnir
  6. Maki Nakayama
  7. James Crooks
  8. Thomas Danhorn
  9. Sonia Leach
  10. Randy Anselment
  11. James Scott-Browne
  12. Laurent Gapin
  13. John Kappler
  1. Howard Hughes Medical Institute, National Jewish Health, United States
  2. University of Colorado School of Medicine, United States
  3. National Jewish Health, United States
  4. La Jolla Institute for Allergy and Immunology, United States
Research Article
  • Cited 10
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Cite this article as: eLife 2017;6:e30918 doi: 10.7554/eLife.30918

Abstract

Mature T cells bearing αβ T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor β chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor α and β chain and, surprisingly, dramatically affected by the non germ line encoded portions of CDR3 of the T cell receptor α chain. Thus, in addition to determining specificity for antigen, the non germline encoded elements of T cell receptors may help the proteins cope with the extremely polymorphic nature of major histocompatibility complex products within the species.

Article and author information

Author details

  1. Philippa Marrack

    Howard Hughes Medical Institute, National Jewish Health, Denver, United States
    For correspondence
    MarrackP@NJHealth.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1883-3687
  2. Sai Harsha Krovi

    Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Daniel Silberman

    Department of Biomedical Research, National Jewish Health, Denver, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Janice White

    Department of Biomedical Research, National Jewish Health, Denver, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Eleanor Kushnir

    Department of Biomedical Research, National Jewish Health, Denver, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Maki Nakayama

    Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. James Crooks

    Division of Biostatistics and Bioinformatics, National Jewish Health, Denver, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Thomas Danhorn

    Division of Biostatistics and Bioinformatics, National Jewish Health, Denver, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3861-8602
  9. Sonia Leach

    Department of Biomedical Research, National Jewish Health, Denver, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Randy Anselment

    Division of Biostatistics and Bioinformatics, National Jewish Health, Denver, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. James Scott-Browne

    La Jolla Institute for Allergy and Immunology, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Laurent Gapin

    Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. John Kappler

    Howard Hughes Medical Institute, National Jewish Health, Denver, United States
    Competing interests
    The authors declare that no competing interests exist.

Funding

National Institutes of Health (AI 18785)

  • Philippa Marrack

National Institutes of Health (AI 092108)

  • Laurent Gapin

National Institutes of Health (AI 103736)

  • Laurent Gapin

Howard Hughes Medical Institute (NA)

  • John Kappler

National Institutes of Health (DK099317)

  • Maki Nakayama

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (AC-2517) of National Jewish Health. The protocol was approved by the Institutional Animal Care and Use Committee of National Jewish Health. Every effort was made to minimize suffering.

Reviewing Editor

  1. Pamela J Bjorkman, California Institute of Technology, United States

Publication history

  1. Received: August 1, 2017
  2. Accepted: November 16, 2017
  3. Accepted Manuscript published: November 17, 2017 (version 1)
  4. Version of Record published: November 24, 2017 (version 2)

Copyright

© 2017, Marrack 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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