The clonal structure and dynamics of the human T cell response to an organic chemical hapten
- University College London, United Kingdom
- University of Manchester, United Kingdom
- 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 .
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Author details
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.
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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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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