{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:05:40Z","timestamp":1789499140569,"version":"build-2803163510"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Antiseizure medications (ASMs) are frequently implicated in T cell-mediated drug hypersensitivity reactions and cause skin tropic pathologies that range in severity from mild rashes to life-threatening systemic syndromes. During the acute stages of the more severe manifestations of these reactions, drug responsive proinflammatory CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells display classical features of Th1 cytokine production (\n                    <jats:italic>e.g.<\/jats:italic>\n                    IFN\u03b3) and cytolysis (\n                    <jats:italic>e.g.<\/jats:italic>\n                    granzyme B, perforin). These T cells may be found locally at the site of pathology (\n                    <jats:italic>e.g.<\/jats:italic>\n                    blister cells\/fluid), as well as systemically (\n                    <jats:italic>e.g.<\/jats:italic>\n                    blood, organs). What is less understood are the long-lived immunological effects of the memory T cell pool following T cell-mediated drug hypersensitivity reactions. In this study, we examine the ASM carbamazepine (CBZ) and the CBZ-reactive memory T cell pool in patients who have a history of either Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) from 3-to-20 years following their initial adverse reaction. We show that\n                    <jats:italic>in vitro<\/jats:italic>\n                    drug restimulation of CBZ-reactive CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells results in a proinflammatory profile and produces a mainly focused, yet private, T cell receptor (TCR) usage amongst human leukocyte antigen (HLA)-B*15:02-positive SJS or TEN patients. Additionally, we show that expression of these CBZ-reactive TCRs in a reporter cell line, lacking endogenous \u03b1\u03b2TCR, recapitulates the features of TCR activation reported for ASM-treated T cell lines\/clones, providing a useful tool for further\u00a0functional validations. Finally, we conduct a comprehensive evaluation of the HLA-B*15:02 immunopeptidome following ASM (or a metabolite) treatment of a HLA-B*15:02-positive B-lymphoblastoid cell line (C1R.B*15:02) and minor perturbation of the peptide repertoire. Collectively, this study shows that the CBZ-reactive T cells characterized require both the drug and HLA-B*15:02 for activation and that reactivation of memory T cells from blood results in a focused\n                    <jats:italic>private<\/jats:italic>\n                    TCR profile in patients with resolved disease.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.653710","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:16:45Z","timestamp":1618186605000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Carbamazepine Induces Focused T Cell Responses in Resolved Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Cases But Does Not Perturb the Immunopeptidome for T Cell Recognition"],"prefix":"10.3389","volume":"12","author":[{"given":"Nicole 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