The clonal structure and dynamics of the human T cell response to an organic chemical hapten

  1. Tahel Ronel
  2. Matthew Harries
  3. Kate Wicks
  4. Theres Oakes
  5. Helen Singleton
  6. Rebecca Dearman
  7. Gavin Maxwell
  8. Benny Chain  Is a corresponding author
  1. University College London, United Kingdom
  2. University of Manchester, United Kingdom
  3. Unilever, United Kingdom

Abstract

Diphenylcyclopropenone (DPC) is an organic chemical hapten which induces allergic contact dermatitis, and is used in treatment of warts, melanoma and alopecia areata. This therapeutic setting therefore provided an opportunity to study T cell receptor (TCR) repertoire changes in response to hapten sensitization in humans. Repeated exposure to DPC induced highly dynamic transient expansions of a polyclonal diverse T cell population. The number of TCRs expanded early after sensitization varies between individuals, and predicts the magnitude of the allergic reaction. The expanded TCRs show preferential TCR V and J gene usage, and consist of clusters of TCRs with similar sequences, two characteristic features of antigen-driven responses. The expanded TCRs share subtle sequence motifs that can be captured using a Dynamic Bayesian Network. These observations suggest the response to DPC is mediated by a polyclonal population of T cells recognizing a small number of dominant antigens.

Data availability

All DNA sequences have been submitted to the Short Read Archive under identifier SUB6567504 .

The following data sets were generated

Article and author information

Author details

  1. Tahel Ronel

    Infection and Immunity, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9513-9181
  2. Matthew Harries

    Faculty of biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
    Competing interests
    No competing interests declared.
  3. Kate Wicks

    Faculty of biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
    Competing interests
    No competing interests declared.
  4. Theres Oakes

    Infection and Immunity, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  5. Helen Singleton

    Faculty of biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
    Competing interests
    No competing interests declared.
  6. Rebecca Dearman

    Faculty of biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
    Competing interests
    No competing interests declared.
  7. Gavin Maxwell

    Safety and Environmental Assurance Centre, Unilever, Bedford, United Kingdom
    Competing interests
    Gavin Maxwell, GM is an employee of Unilever PLC. Apart from GM's contribution (see author contributions) the funder was not involved in the study design, collection, analysis, and interpretation of data, the writing of this article or the decision to submit it for publication..
  8. Benny Chain

    Infection and Immunity, University College London, London, United Kingdom
    For correspondence
    b.chain@ucl.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7417-3970

Funding

Unilever

  • Benny Chain

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

Ethics

Human subjects: The protocol was approved by the University College London Hospital Ethics Committee 06/Q0502/92. A total of 34 patients were recruited to this study (NRES Ethics Committee East of England - Cambridgeshire and Hertfordshire [14/EE/1067]). Participants were recruited from patients who had been diagnosed with alopecia, were aged between 18 and 70, identified as suitable for DPC treatment by a consultant dermatologist, and were now attending their first visit to the Alopecia Clinic at Salford Royal Hospital for DPC therapy. This study ran alongside patients' prescribed DPC treatment (weekly doses of DPC to the scalp to induce inflammation and hair regrowth). All participants gave their informed consent to participate, and were free to withdraw from the study at any time and for any reason without affecting their treatment. Patients were excluded from the study if they were pregnant.

Reviewing Editor

  1. Armita Nourmohammad, University of Washington, United States

Publication history

  1. Received: December 27, 2019
  2. Accepted: January 12, 2021
  3. Accepted Manuscript published: January 12, 2021 (version 1)
  4. Version of Record published: February 12, 2021 (version 2)

Copyright

© 2021, Ronel 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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  1. Tahel Ronel
  2. Matthew Harries
  3. Kate Wicks
  4. Theres Oakes
  5. Helen Singleton
  6. Rebecca Dearman
  7. Gavin Maxwell
  8. Benny Chain
(2021)
The clonal structure and dynamics of the human T cell response to an organic chemical hapten
eLife 10:e54747.
https://doi.org/10.7554/eLife.54747

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