{
  "abstract": "The initiation of T-cell-mediated drug hypersensitivity reaction requires the formation of a human leukocyte antigen (HLA)-peptide-drug-T-cell receptor (TCR) complex. While specific interactions between HLA molecules and drug antigens are well-defined, the characteristics of drug binding to the TCR are unclear. Herein, we sequenced the TCR mRNAs of T-cells that express drug-specific HLAs (including HLA-A*31:01, HLA-B*15:02, and HLA-B*13:01) and exhibit drug-specific immune responses against carbamazepine, sulfamethoxazole, and dapsone. This study included a total of 46 in vitro-generated monoclonal drug-specific (CD4+ and CD8+) T-cell clones. The T-cell clones were characterized for their drug-specific immune response, including HLA restriction properties, interferon-γ secretion, and cross-reactive responses. RNA isolated from these cells was used for TCR library preparation and subsequent long-read sequencing analyses. T-cell characterization studies showed different drug-responsiveness properties among the clones. TCR sequencing revealed wide heterogeneity among drug-specific T-cells. Only TCR Vβ (TRBV) and TCR Jβ (TRBJ) segments of CD4+ T-cell clones displayed noticeable shared characteristics. A YEQYF residue on CDR3β, which correlates with the preferential use of TRBJ2-7, was identified in 5 out of 16 CD4+ carbamazepine-specific clones. However, CD8+ drug-specific clones showed no preferential usage of TCR α/β. Sequence alignment analyses among clones with similar or different drug-responsiveness properties also showed no evidence of structure-function correlation. In summary, TCR specificity against drug antigens appears to be nonrestrictive, suggesting that the extent of possible binding and its key determinants are not rigid.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla90110, Thailand.",
    "Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, LiverpoolL69 3GE, U.K.",
    "Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok10400, Thailand.",
    "Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok10400, Thailand.",
    "Department of Clinical Chemistry, Faculty of Medical Technology, Huachiew Chalermprakiet University, Samut Prakan10540, Thailand.",
    "Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan250022, China.",
    "Department of Medical Laboratory Sciences, College of Applied Medical Sciences in Alquwayiyah, Shaqra University, Shaqra, Riyadh Province15526, Saudi Arabia.",
    "Division of Pharmacy, Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University, Songkhla90110, Thailand.",
    "Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla90110, Thailand.",
    "Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, 90110Songkhla, Thailand.",
    "Faculty of Pharmaceutical Sciences, Burapha University, Saensuk, Mueang, Chonburi20131, Thailand."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Kanoot Jaruthamsophon",
      "orcid": "0000-0003-1563-0024"
    },
    {
      "affs": [
        1
      ],
      "name": "Paul J Thomson",
      "orcid": "0000-0001-5431-0459"
    },
    {
      "affs": [
        1,
        2,
        3,
        4
      ],
      "name": "Jirawat Pratoomwun"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Qing Zhao",
      "orcid": "0000-0003-4553-2871"
    },
    {
      "affs": [
        1,
        6
      ],
      "name": "Mubarak Almutairi"
    },
    {
      "affs": [
        7
      ],
      "name": "Antida Sangiemchoey"
    },
    {
      "affs": [
        8
      ],
      "name": "Araya Yeunyongviwat"
    },
    {
      "affs": [
        9
      ],
      "name": "Kanitpong Phabphal"
    },
    {
      "affs": [
        5
      ],
      "name": "Hong Liu"
    },
    {
      "affs": [
        5
      ],
      "name": "Furen Zhang"
    },
    {
      "affs": [
        5
      ],
      "name": "Yonghu Sun"
    },
    {
      "affs": [
        1,
        2,
        3,
        10
      ],
      "name": "Chonlaphat Sukasem"
    },
    {
      "affs": [
        1
      ],
      "name": "Munir Pirmohamed"
    },
    {
      "affs": [
        1
      ],
      "name": "Dean J Naisbitt",
      "orcid": "0000-0003-4107-7832"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cw48p15ghyx52.bib",
  "cited_by": 0,
  "doi": "10.1021/acs.chemrestox.6c00152",
  "fulltext_url": "https://europepmc.org/articles/PMC13599470",
  "id": "cw48p15ghyx52",
  "issns": [
    "0893-228X",
    "1520-5010"
  ],
  "landing_url": "https://europepmc.org/article/MED/42915728",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2736|Drug-Induced Adverse Reactions"
    ]
  ],
  "openalex": "W7203672209",
  "pdf_url": "https://europepmc.org/articles/PMC13599470?pdf=render",
  "pmcid": "PMC13599470",
  "pmid": "42915728",
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/cw48p15ghyx52.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:02Z",
      "native_id": "MED:42915728",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42915728"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2736|Drug-Induced Adverse Reactions",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Shared and Distinct T-Cell Receptor Characteristics of CD4+ and CD8+ Drug-Specific T-Cells In Vitro Generated from Healthy Donors and Hypersensitive Patients.",
  "title_text": "Shared and Distinct T-Cell Receptor Characteristics of CD4+ and CD8+ Drug-Specific T-Cells In Vitro Generated from Healthy Donors and Hypersensitive Patients.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:02Z",
  "url": "https://research.draconitic.com/paper/cw48p15ghyx52",
  "venue": "Chemical research in toxicology",
  "versions": []
}