The clonal structure and dynamics of the human T cell response to an organic chemical hapten
Diphenylcyclopropenone (DPC) is an organic chemical hapten which induces allergic contact dermatitis and is used in the 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 hapte...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-01-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/54747 |
| _version_ | 1828168866371469312 |
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| author | Tahel Ronel Matthew Harries Kate Wicks Theres Oakes Helen Singleton Rebecca Dearman Gavin Maxwell Benny Chain |
| author_facet | Tahel Ronel Matthew Harries Kate Wicks Theres Oakes Helen Singleton Rebecca Dearman Gavin Maxwell Benny Chain |
| author_sort | Tahel Ronel |
| collection | DOAJ |
| description | Diphenylcyclopropenone (DPC) is an organic chemical hapten which induces allergic contact dermatitis and is used in the 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. |
| first_indexed | 2024-04-12T02:41:50Z |
| format | Article |
| id | doaj.art-34a29ae1bbed42fa8f0805557632c0c1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:41:50Z |
| publishDate | 2021-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-34a29ae1bbed42fa8f0805557632c0c12022-12-22T03:51:17ZengeLife Sciences Publications LtdeLife2050-084X2021-01-011010.7554/eLife.54747The clonal structure and dynamics of the human T cell response to an organic chemical haptenTahel Ronel0https://orcid.org/0000-0002-9513-9181Matthew Harries1Kate Wicks2Theres Oakes3Helen Singleton4Rebecca Dearman5Gavin Maxwell6Benny Chain7https://orcid.org/0000-0002-7417-3970Division of Infection and Immunity, University College London, London, United Kingdom; Cancer Institute, University College London, London, United KingdomFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom; Salford Royal NHS Foundation Trust (Dermatology Centre), Salford, United KingdomFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomDivision of Infection and Immunity, University College London, London, United KingdomFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomFaculty of Biology, Medicine and Health, University of Manchester, Manchester, United KingdomSafety and Environmental Assurance Centre, Unilever, Colworth Science Park, Bedford, United KingdomDivision of Infection and Immunity, University College London, London, United Kingdom; Department of Computer Science, University College London, London, United KingdomDiphenylcyclopropenone (DPC) is an organic chemical hapten which induces allergic contact dermatitis and is used in the 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.https://elifesciences.org/articles/54747T cell receptorrepertoirecontact dermatitispatch testcdr3 motifBayesian network |
| spellingShingle | Tahel Ronel Matthew Harries Kate Wicks Theres Oakes Helen Singleton Rebecca Dearman Gavin Maxwell Benny Chain The clonal structure and dynamics of the human T cell response to an organic chemical hapten eLife T cell receptor repertoire contact dermatitis patch test cdr3 motif Bayesian network |
| title | The clonal structure and dynamics of the human T cell response to an organic chemical hapten |
| title_full | The clonal structure and dynamics of the human T cell response to an organic chemical hapten |
| title_fullStr | The clonal structure and dynamics of the human T cell response to an organic chemical hapten |
| title_full_unstemmed | The clonal structure and dynamics of the human T cell response to an organic chemical hapten |
| title_short | The clonal structure and dynamics of the human T cell response to an organic chemical hapten |
| title_sort | clonal structure and dynamics of the human t cell response to an organic chemical hapten |
| topic | T cell receptor repertoire contact dermatitis patch test cdr3 motif Bayesian network |
| url | https://elifesciences.org/articles/54747 |
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