{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T01:55:45Z","timestamp":1790819745255,"version":"4.1.0"},"reference-count":45,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T00:00:00Z","timestamp":1610409600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007190","name":"Unilever","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.7554\/elife.54747","type":"journal-article","created":{"date-parts":[[2021,1,12]],"date-time":"2021-01-12T13:37:55Z","timestamp":1610458675000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.54747","source":"Crossref","is-referenced-by-count":13,"title":["The clonal structure and dynamics of the human T cell response to an organic chemical hapten"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9513-9181","authenticated-orcid":true,"given":"Tahel","family":"Ronel","sequence":"first","affiliation":[{"name":"Division of Infection and Immunity, University College London, London, United Kingdom"},{"name":"Cancer Institute, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Harries","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom"},{"name":"Salford Royal NHS Foundation Trust (Dermatology Centre), Salford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Wicks","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theres","family":"Oakes","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Singleton","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Dearman","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin","family":"Maxwell","sequence":"additional","affiliation":[{"name":"Safety and Environmental Assurance Centre, Unilever, Colworth Science Park, Bedford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7417-3970","authenticated-orcid":true,"given":"Benny","family":"Chain","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, University College London, London, United Kingdom"},{"name":"Department of Computer Science, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2021,1,12]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1002\/cyto.a.20643","article-title":"Phenotype and function of human T lymphocyte subsets: consensus and issues","volume":"73A","author":"Appay","year":"2008","journal-title":"Cytometry Part A"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1111\/j.1365-2133.1989.tb04166.x","article-title":"Allergic and irritant contact dermatitis compared in the treatment of alopecia totalis and universalis A comparison of the value of topical diphencyprone and tretinoin gel","volume":"120","author":"Ashworth","year":"1989","journal-title":"British Journal of Dermatology"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.yrtph.2015.11.013","article-title":"Skin sensitization quantitative risk assessment: a review of underlying assumptions","volume":"74","author":"Basketter","year":"2016","journal-title":"Regulatory Toxicology and Pharmacology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.cell.2014.12.020","article-title":"Variation in the human immune system is largely driven by non-heritable influences","volume":"160","author":"Brodin","year":"2015","journal-title":"Cell"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1046\/j.1365-2133.1999.02978.x","article-title":"Recalcitrant viral warts treated by diphencyprone immunotherapy","volume":"141","author":"Buckley","year":"1999","journal-title":"British Journal of Dermatology"},{"key":"bib6","article-title":"The igraph software package for complex network research","volume":"2006","author":"Csardi","year":"2006","journal-title":"Inter Journal Complex Sy"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/B978-1-4832-8287-9.50010-4","article-title":"Dynamic network models for forecasting","volume":"1992","author":"Dagum","year":"1992","journal-title":"Uncertainty in Artificial Intelligence"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/nature22383","article-title":"Quantifiable predictive features define epitope-specific T cell receptor repertoires","volume":"547","author":"Dash","year":"2017","journal-title":"Nature"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1749-6632.1995.tb44477.x","article-title":"T-cell receptor V-region usage and antigen specificity the cytochrome c model system","volume":"756","author":"Davis","year":"1995","journal-title":"Annals of the New York Academy of Sciences"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"4517","DOI":"10.1128\/JVI.03474-14","article-title":"Dynamics of the cytotoxic T cell response to a model of acute viral infection","volume":"89","author":"DeWitt","year":"2015","journal-title":"Journal of Virology"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"8218","DOI":"10.4049\/jimmunol.175.12.8218","article-title":"Cytomegalovirus-specific CD4+ T cells in healthy carriers are continuously driven to replicative exhaustion","volume":"175","author":"Fletcher","year":"2005","journal-title":"The Journal of Immunology"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.toxlet.2005.10.008","article-title":"Contact sensitisation and allergic contact dermatitis: immunobiological mechanisms","volume":"162","author":"Friedmann","year":"2006","journal-title":"Toxicology Letters"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1111\/j.1365-2133.2007.08162.x","article-title":"The relationships between exposure dose and response in induction and elicitation of contact hypersensitivity in humans","volume":"157","author":"Friedmann","year":"2007","journal-title":"British Journal of Dermatology"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/nature22976","article-title":"Identifying specificity groups in the T cell receptor repertoire","volume":"547","author":"Glanville","year":"2017","journal-title":"Nature"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1111\/bjd.16489","article-title":"Diphenylcyclopropenone for Alopecia Areata: a U.K. survey","volume":"70","author":"Karanovic","year":"2018","journal-title":"British Journal of Dermatology"},{"key":"bib16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v011.i09","article-title":"Kernlab - An S4 Package for Kernel Methods in R","volume":"11","author":"Karatzoglou","year":"2004","journal-title":"Journal of Statistical Software"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.tox.2011.11.007","article-title":"Allergic contact dermatitis: a commentary on the relationship between T lymphocytes and skin sensitising potency","volume":"291","author":"Kimber","year":"2012","journal-title":"Toxicology"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"3276","DOI":"10.1093\/bioinformatics\/btu531","article-title":"AliView: a fast and lightweight alignment viewer and editor for large datasets","volume":"30","author":"Larsson","year":"2014","journal-title":"Bioinformatics"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1001\/jamadermatol.2018.2312","article-title":"Hair regrowth outcomes of contact immunotherapy for patients with Alopecia Areata: a systematic review and Meta-analysis","volume":"154","author":"Lee","year":"2018","journal-title":"JAMA Dermatology"},{"key":"bib20","article-title":"BayesNet, Comprehensive TeX Archive Network (CTAN)","volume-title":"Github","author":"Luttinen","year":"2013","unstructured":"Luttinen J, Dietz L. 2013. BayesNet, Comprehensive TeX Archive Network (CTAN). Github. 1.0. https:\/\/github.com\/jluttine\/tikz-bayesnet."},{"key":"bib21","doi-asserted-by":"publisher","first-page":"473","DOI":"10.14573\/altex.2013.4.473","article-title":"From pathways to people: applying the adverse outcome pathway (AOP) for skin sensitization to risk assessment","volume":"30","author":"MacKay","year":"2013","journal-title":"Altex"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1177\/026119290803600510","article-title":"Application of a systems biology approach to skin allergy risk assessment","volume":"36","author":"Maxwell","year":"2008","journal-title":"Alternatives to Laboratory Animals"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1111\/bjd.14949","article-title":"Repeated monthly epicutaneous challenges with diphenylcyclopropenone result in a clinically reproducible level of contact allergy in de novo sensitized individuals","volume":"176","author":"Mose","year":"2017","journal-title":"British Journal of Dermatology"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1111\/exd.13345","article-title":"The gene expression and immunohistochemical time-course of diphenylcyclopropenone-induced contact allergy in healthy humans following repeated epicutaneous challenges","volume":"26","author":"Mose","year":"2017","journal-title":"Experimental Dermatology"},{"key":"bib25","article-title":"The bayes net toolbox for MATLAB","volume":"33","author":"Murphy","year":"2001","journal-title":"Comput Science"},{"key":"bib26","article-title":"Dynamic bayesian networks: representation, inference and learning","author":"Murphy","year":"2002","unstructured":"Murphy KP. 2002. Dynamic bayesian networks: representation, inference and learning. Thesis for: PhD."},{"key":"bib27","volume-title":"Modelling Gene Expression Data Using Dynamic Bayesian Networks","author":"Murphy","year":"1999"},{"key":"bib28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01267","article-title":"Quantitative characterization of the T cell receptor repertoire of na\u00efve and memory subsets using an integrated experimental and computational pipeline which is robust, economical, and versatile","volume":"8","author":"Oakes","year":"2017","journal-title":"Frontiers in Immunology"},{"key":"bib29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00162","article-title":"The T cell response to the contact sensitizer paraphenylenediamine is characterized by a polyclonal diverse repertoire of Antigen-Specific receptors","volume":"8","author":"Oakes","year":"2017","journal-title":"Frontiers in Immunology"},{"key":"bib30","volume-title":"Probabilistic Reasoning in Intelligent Systems : Networks of Plausible Inference","author":"Pearl","year":"1988"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"12704","DOI":"10.1073\/pnas.1809642115","article-title":"Precise tracking of vaccine-responding T cell clones reveals convergent and personalized response in identical twins","volume":"115","author":"Pogorelyy","year":"2018","journal-title":"PNAS"},{"key":"bib32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000314","article-title":"Detecting T cell receptors involved in immune responses from single repertoire snapshots","volume":"17","author":"Pogorelyy","year":"2019","journal-title":"PLOS Biology"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"2030","DOI":"10.1111\/jdv.14422","article-title":"Diphenylcyclopropenone for the treatment of cutaneous in-transit melanoma metastases - results of a prospective, non-randomized, single-centre study","volume":"31","author":"Read","year":"2017","journal-title":"Journal of the European Academy of Dermatology and Venereology"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.comtox.2018.10.004","article-title":"Probabilistic prediction of human skin sensitiser potency for use in next generation risk assessment","volume":"9","author":"Reynolds","year":"2019","journal-title":"Computational Toxicology"},{"key":"bib35","doi-asserted-by":"crossref","DOI":"10.1017\/CBO9780511809682","volume-title":"Kernel Methods for Pattern Analysis","author":"Shawe-Taylor","year":"2004"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1111\/cod.12486","article-title":"Anti-hapten antibodies in response to skin sensitization","volume":"74","author":"Singleton","year":"2016","journal-title":"Contact Dermatitis"},{"key":"bib37","first-page":"12","article-title":"Diphenylcyclopropenone - a new strong contact sensitizer (author\u2019s transl)","volume":"29","author":"Stute","year":"1981","journal-title":"Dermatosen in Beruf Und Umwelt. Occupation and Environment"},{"key":"bib38","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00430","article-title":"Specificity, privacy, and degeneracy in the CD4 T cell receptor repertoire following immunization","volume":"8","author":"Sun","year":"2017","journal-title":"Frontiers in Immunology"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"3181","DOI":"10.1093\/bioinformatics\/btu523","article-title":"Tracking global changes induced in the CD4 T-cell receptor repertoire by immunization with a complex antigen using short stretches of CDR3 protein sequence","volume":"30","author":"Thomas","year":"2014","journal-title":"Bioinformatics"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1007\/s12016-017-8620-9","article-title":"Alopecia Areata: a comprehensive review of pathogenesis and management","volume":"54","author":"Tr\u00fceb","year":"2018","journal-title":"Clinical Reviews in Allergy & Immunology"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/978-1-4939-8885-3_2","article-title":"An economical, quantitative, and robust protocol for High-Throughput T cell receptor sequencing from tumor or blood","volume":"1884","author":"Uddin","year":"2019","journal-title":"Methods in Molecular Biology"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/bs.mie.2019.05.054","article-title":"Quantitative analysis of the T cell receptor repertoire","volume":"629","author":"Uddin","year":"2019","journal-title":"Methods in Enzymology"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1111\/j.1398-9995.2012.02802.x","article-title":"The contact sensitizer diphenylcyclopropenone has adjuvant properties in mice and potential application in epicutaneous immunotherapy","volume":"67","author":"von Moos","year":"2012","journal-title":"Allergy"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1016\/S0190-9622(87)70244-8","article-title":"Assessment of diphenylcyclopropenone for photochemically induced mutagenicity in the ames assay","volume":"17","author":"Wilkerson","year":"1987","journal-title":"Journal of the American Academy of Dermatology"},{"key":"bib45","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-49","article-title":"A dynamic bayesian network approach to protein secondary structure prediction","volume":"9","author":"Yao","year":"2008","journal-title":"BMC Bioinformatics"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/54747\/elife-54747-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/54747\/elife-54747-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/54747","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T20:59:15Z","timestamp":1697057955000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/54747"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,12]]},"references-count":45,"alternative-id":["10.7554\/eLife.54747"],"URL":"https:\/\/doi.org\/10.7554\/elife.54747","archive":["CLOCKSS"],"relation":{"is-supplemented-by":[{"id-type":"accession","id":"PRJNA592875","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.54747.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.54747.sa1","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,12]]},"article-number":"e54747"}}