title: The T Cell Response to the Contact Sensitizer Paraphenylenediamine Is Characterized by a Polyclonal Diverse Repertoire of Antigen-Specific Receptors.
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 thein vitrorecall 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 antigenin 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 ofin vitroexpansion.
authors.affiliation: Division of Infection and Immunity, UCL , London , UK.
authors.forename: Theres
authors.initials: T
authors.lastname: Oakes
authors.affiliation: Faculty of Life Sciences, University of Manchester , Manchester , UK.
authors.forename: Amy Lee
authors.initials: AL
authors.lastname: Popple
authors.affiliation: Contact Dermatitis Investigation Unit, Salford Royal NHS Foundation Trust , Manchester , UK.
authors.forename: Jason
authors.initials: J
authors.lastname: Williams
authors.affiliation: Division of Infection and Immunity, UCL , London , UK.
authors.forename: Katharine
authors.initials: K
authors.lastname: Best
authors.affiliation: Division of Infection and Immunity, UCL , London , UK.
authors.forename: James M
authors.initials: JM
authors.lastname: Heather
authors.affiliation: Division of Infection and Immunity, UCL , London , UK.
authors.forename: Mazlina
authors.initials: M
authors.lastname: Ismail
authors.affiliation: Unilever Safety and Environmental Assurance Centre, Colworth Science Park , Sharnbrook , UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Maxwell
authors.affiliation: Unilever Safety and Environmental Assurance Centre, Colworth Science Park , Sharnbrook , UK.
authors.forename: Nichola
authors.initials: N
authors.lastname: Gellatly
authors.affiliation: Faculty of Life Sciences, University of Manchester , Manchester , UK.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Dearman
authors.affiliation: Faculty of Life Sciences, University of Manchester , Manchester , UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Kimber
authors.affiliation: Division of Infection and Immunity, UCL , London , UK.
authors.forename: Benny
authors.initials: B
authors.lastname: Chain
keywords: T cell immunity; T cell receptor repertoire; allergic contact dermatitis; paraphenylenediamine; skin sensitizer