Identification of Drug-Specific Public TCR Driving Severe Cutaneous Adverse Reactions

In a study from 2019, researchers investigated the T cell receptor (TCR) repertoire in patients with severe cutaneous adverse reactions (SCAR), including Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are potentially life-threatening drug hypersensitivities. They identified a public αβTCR in the cytotoxic T lymphocytes of patients with carbamazepine-induced SJS/TEN that showed specificity to the drug and a bias for the HLA-B*15:02 allele. This TCR was found to have a binding affinity for carbamazepine and its structural analogs, suggesting it mediates the immune response associated with SCAR. When T cells expressing this public αβTCR were transferred to HLA-B*15:02 transgenic mice that were administered carbamazepine orally, the mice developed multi-organ injuries and symptoms similar to SCAR, including hair loss, erythema, increased inflammatory lymphocytes in the skin and blood, and liver and kidney dysfunction. These findings highlight the crucial role of TCR in mediating SCAR and suggest avenues for potential clinical applications and therapeutic development. The number of patients enrolled in the study was not specified.