Journal article
Identification of drug-specific public TCR driving severe cutaneous adverse reactions
Nature Communications, Vol.10(1), art. no. 3569
2019
Abstract
Drug hypersensitivity such as severe cutaneous adverse reactions (SCAR), including Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), could be life-threatening. Here, we enroll SCAR patients to investigate the T cell receptor (TCR) repertoire by next-generation sequencing. A public αβTCR is identified from the cytotoxic T lymphocytes of patients with carbamazepine-SJS/TEN, with its expression showing drug/phenotype-specificity and an bias for HLA-B*15:02. This public αβTCR has binding affinity for carbamazepine and its structural analogs, thereby mediating the immune response. Adoptive transfer of T cell expressing this public αβTCR to HLA-B*15:02 transgenic mice receiving oral administration of carbamazepine induces multi-organ injuries and symptoms mimicking SCAR, including hair loss, erythema, increase of inflammatory lymphocytes in the skin and blood, and liver and kidney dysfunction. Our results not only demonstrate an essential role of TCR in the immune synapse mediating SCAR, but also implicate potential clinical applications and development of therapeutics.
Details
- Title
- Identification of drug-specific public TCR driving severe cutaneous adverse reactions
- Authors/Creators
- R-Y Pan (Author/Creator) - Chang Gung Memorial HospitalM-T Chu (Author/Creator) - Chang Gung Memorial HospitalC-W Wang (Author/Creator) - Chang Gung Memorial HospitalY-S Lee (Author/Creator) - Ming Chuan UniversityF Lemonnier (Author/Creator) - Institut CochinA.W. Michels (Author/Creator) - University of Colorado DenverR. Schutte (Author/Creator) - Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32611, USAD.A. Ostrov (Author/Creator) - Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32611, USAC-B Chen (Author/Creator) - Chang Gung UniversityE.J. Phillips (Author/Creator) - Vanderbilt UniversityS.A. Mallal (Author/Creator) - Vanderbilt UniversityM. Mockenhaupt (Author/Creator) - University of FreiburgT. Bellón (Author/Creator) - Hospital Universitario La PazW. Tassaneeyakul (Author/Creator) - Khon Kaen UniversityK.D. White (Author/Creator) - Vanderbilt UniversityJ-C Roujeau (Author/Creator) - Emeritus Professor of Dermatology, Université Paris-Est Créteil (UPEC), Créteil, 94000, France.W-H Chung (Author/Creator) - Chang Gung Memorial HospitalS-L Hung (Author/Creator)
- Publication Details
- Nature Communications, Vol.10(1), art. no. 3569
- Publisher
- Springer Nature
- Identifiers
- 991005544054607891
- Copyright
- © 2019 Springer Nature Publishing AG
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.265 Dermatology - Skin Allergies
- 1.265.1140 Drug Hypersensitivity
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology