1. Immunology and Inflammation
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Somatic hypermutation of T cell receptor α chain contributes to selection in nurse shark thymus

  1. Jeannine A Ott
  2. Caitlin D Castro
  3. Thaddeus C Deiss
  4. Yuko Ohta
  5. Martin F Flajnik
  6. Michael F Criscitiello  Is a corresponding author
  1. Texas A&M University, United States
  2. University of Maryland, United States
Research Article
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Cite this article as: eLife 2018;7:e28477 doi: 10.7554/eLife.28477

Abstract

Since the discovery of the T cell receptor (TcR), immunologists have assigned somatic hypermutation (SHM) as a mechanism employed solely by B cells to diversify their antigen receptors. Remarkably, we found SHM acting in the thymus on α chain locus of shark TcR. SHM in developing shark T cells likely is catalyzed by activation-induced cytidine deaminase (AID) and results in both point and tandem mutations that accumulate non-conservative amino acid replacements within complementarity-determining regions (CDRs). Mutation frequency at TcRα was as high as that seen at B cell receptor loci (BcR) in sharks and mammals, and the mechanism of SHM shares unique characteristics first detected at shark BcR loci. Additionally, fluorescence in situ hybridization showed the strongest AID expression in thymic corticomedullary junction and medulla. We suggest that TcRα utilizes SHM to broaden diversification of the primary αβ T cell repertoire in sharks, the first reported use in vertebrates.

Data availability

T cell receptor sequences have been deposited in Genbank of NCBI.Alpha KY189332-KY189354 and KY366469-KY355487;Beta KY351708-KY366487;Gamma KY351639-KY351707;Delta KY346705-KY346816

Article and author information

Author details

  1. Jeannine A Ott

    Comparative Immunogenetics Laboratory, Department of Veterinary Pathobiology College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3537-8631
  2. Caitlin D Castro

    Department of Microbiology and Immunology, University of Maryland, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Thaddeus C Deiss

    Comparative Immunogenetics Laboratory, Department of Veterinary Pathobiology College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yuko Ohta

    Department of Microbiology and Immunology, University of Maryland, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Martin F Flajnik

    Department of Microbiology and Immunology, University of Maryland, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Michael F Criscitiello

    Comparative Immunogenetics Laboratory, Department of Veterinary Pathobiology College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, United States
    For correspondence
    MCRISCITIELLO@CVM.TAMU.EDU
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4262-7832

Funding

National Science Foundation (IOS 1257829)

  • Michael F Criscitiello

National Institute of Allergy and Infectious Diseases (R01OD0549)

  • Martin F Flajnik

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

Ethics

Animal experimentation: These studies were carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Animal Care and Use Committees at Texas A&M University and University of Maryland School of Medicine. Experiments in the Criscitiello lab were performed under Texas A&M University Institutional Biosafety Committee permit IBC 2014-293 and Animal Use Protocol 2015-0374.

Reviewing Editor

  1. David G Schatz, Yale University School of Medicine, United States

Publication history

  1. Received: May 9, 2017
  2. Accepted: April 16, 2018
  3. Accepted Manuscript published: April 17, 2018 (version 1)
  4. Version of Record published: May 2, 2018 (version 2)
  5. Version of Record updated: May 2, 2018 (version 3)

Copyright

© 2018, Ott 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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