TY - JOUR TI - The clonal structure and dynamics of the human T cell response to an organic chemical hapten AU - Ronel, Tahel AU - Harries, Matthew AU - Wicks, Kate AU - Oakes, Theres AU - Singleton, Helen AU - Dearman, Rebecca AU - Maxwell, Gavin AU - Chain, Benny A2 - Nourmohammad, Armita A2 - Walczak, Aleksandra M A2 - Elhanati, Yuval A2 - Mariotti-Ferrandiz, Encarnita VL - 10 PY - 2021 DA - 2021/01/12 SP - e54747 C1 - eLife 2021;10:e54747 DO - 10.7554/eLife.54747 UR - https://doi.org/10.7554/eLife.54747 AB - 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. KW - T cell receptor KW - repertoire KW - contact dermatitis KW - patch test KW - cdr3 motif KW - Bayesian network JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -