Shared and Distinct T-Cell Receptor Characteristics of CD4+ and CD8+ Drug-Specific T-Cells In Vitro Generated from Healthy Donors and Hypersensitive Patients.
11 affiliations
- 1Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla90110, Thailand.
- 2Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, LiverpoolL69 3GE, U.K.
- 3Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok10400, Thailand.
- 4Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok10400, Thailand.
- 5Department of Clinical Chemistry, Faculty of Medical Technology, Huachiew Chalermprakiet University, Samut Prakan10540, Thailand.
- 6Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan250022, China.
- 7Department of Medical Laboratory Sciences, College of Applied Medical Sciences in Alquwayiyah, Shaqra University, Shaqra, Riyadh Province15526, Saudi Arabia.
- 8Division of Pharmacy, Songklanagarind Hospital, Faculty of Medicine, Prince of Songkla University, Songkhla90110, Thailand.
- 9Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Songkhla90110, Thailand.
- 10Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, 90110Songkhla, Thailand.
- 11Faculty of Pharmaceutical Sciences, Burapha University, Saensuk, Mueang, Chonburi20131, Thailand.
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.
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BibTeX
@article{jaruthamsophon2026shared,
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.}},
author = {Kanoot Jaruthamsophon and Paul J Thomson and Jirawat Pratoomwun and Qing Zhao and Mubarak Almutairi and Antida Sangiemchoey and Araya Yeunyongviwat and Kanitpong Phabphal and Hong Liu and Furen Zhang and Yonghu Sun and Chonlaphat Sukasem and Munir Pirmohamed and Dean J Naisbitt},
journal = {Chemical research in toxicology},
year = {2026},
month = sep,
doi = {10.1021/acs.chemrestox.6c00152},
url = {https://europepmc.org/article/MED/42915728},
note = {CC BY},
}
RIS
TY - JOUR
TI - Shared and Distinct T-Cell Receptor Characteristics of CD4+ and CD8+ Drug-Specific T-Cells In Vitro Generated from Healthy Donors and Hypersensitive Patients.
AU - Kanoot Jaruthamsophon
AU - Paul J Thomson
AU - Jirawat Pratoomwun
AU - Qing Zhao
AU - Mubarak Almutairi
AU - Antida Sangiemchoey
AU - Araya Yeunyongviwat
AU - Kanitpong Phabphal
AU - Hong Liu
AU - Furen Zhang
AU - Yonghu Sun
AU - Chonlaphat Sukasem
AU - Munir Pirmohamed
AU - Dean J Naisbitt
PY - 2026
DA - 2026/09/01
JO - Chemical research in toxicology
DO - 10.1021/acs.chemrestox.6c00152
UR - https://europepmc.org/article/MED/42915728
AB - 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.
SN - 0893-228X
SN - 1520-5010
ER -