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The T Cell Response to the Contact Sensitizer Paraphenylenediamine Is Characterized by a Polyclonal Diverse Repertoire of Antigen-Specific Receptors

Oakes, T; Popple, AL; Williams, J; Best, K; Heather, JM; Ismail, M; Maxwell, G; ... Chain, B; + view all (2017) The T Cell Response to the Contact Sensitizer Paraphenylenediamine Is Characterized by a Polyclonal Diverse Repertoire of Antigen-Specific Receptors. Frontiers in Immunology , 8 , Article 162. 10.3389/fimmu.2017.00162. Green open access

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Abstract

Paraphenylenediamine (PPD) is a common component of hair dyes and black henna tattoos and can cause skin sensitization and allergic contact dermatitis (ACD). The cutaneous inflammatory reaction associated with ACD is driven by both CD4+ and CD8+ T cells. However, the characteristics of such responses with respect to clonal breadth and magnitude are poorly defined. In this study, we have characterized the in vitro recall response of peripheral blood T cells prepared from PPD-allergic individuals to a PPD-human serum albumin (HSA) conjugate (PPD-HSA). Quantitative high throughput sequencing was used to characterize the changes in the repertoire of T cell receptor (TCR) α and β genes after exposure to antigen in vitro. The PPD conjugate induced expansion of T cells carrying selected TCRs, with around 800 sequences (around 1%) being 8 or more times as abundant after culture than before. The expanded sequences showed strong skewing of V and J usage, consistent with an antigen-driven clonal expansion. The complementarity-determining region 3 sequences of the expanded TCRs could be grouped into several families of related amino acid sequence, but the overall diversity of the expanded sample was not much less than that of a random sample of the same size. The results suggest a model in which PPD-HSA conjugate stimulates a broad diversity of TCRs, with a wide range of stimulation strengths, which manifest as different degrees of in vitro expansion.

Type: Article
Title: The T Cell Response to the Contact Sensitizer Paraphenylenediamine Is Characterized by a Polyclonal Diverse Repertoire of Antigen-Specific Receptors
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2017.00162
Publisher version: http://doi.org/10.3389/fimmu.2017.00162
Language: English
Additional information: © 2017 Oakes, Popple, Williams, Best, Heather, Ismail, Maxwell, Gellatly, Dearman, Kimber and Chain. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: T cell immunity, T cell receptor repertoire, allergic contact dermatitis, paraphenylenediamine, skin sensitizer
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: http://discovery.ucl.ac.uk/id/eprint/1545131
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