Characterization of Teicoplanin-Specific T-Cells from Drug Naïve Donors Expressing HLA-A*32:01.

Characterization of Teicoplanin-Specific T-Cells from Drug Naïve Donors Expressing HLA-A*32:01.
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来自表达HLA-A*32:01的未用药供体的替考拉宁特异性T细胞的表征。

DOI:
10.1021/acs.chemrestox.1c00425
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发表时间:
2022-02-21
影响因子:
4.1
通讯作者:
Naisbitt, Dean J.
Naisbitt, Dean J.
中科院分区:
医学3区
文献类型:
--
作者:
Gardner, Joshua;Ogese, Monday;Betts, Catherine J.;Pirmohamed, Munir;Naisbitt, Dean J.

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替考拉宁是一种糖肽抗生素,用于对抗革兰氏阳性细菌感染,最近被认为与药物不良反应的发生有关,特别是在之前接触万古霉素之后。在这项研究中,我们从健康志愿者中产生了表达HLA-A*32:01的替考拉宁特异性单抗T细胞群体,并确定了T细胞激活和HLA等位基因限制的途径。替考拉宁反应的T细胞是CD8+、HLAI类限制性T细胞,并在增殖和细胞因子/细胞溶解分子(颗粒酶B、穿孔素和FasL)释放实验中与脂糖肽达托霉素发生交叉反应。这些数据表明,替考拉宁能激活人类白细胞抗原A*32:01阳性献血者的T细胞,这可能在替考拉宁引起的不良反应的发病机制中起一定作用。
Teicoplanin is a glycopeptide antibiotic deployed to combat Gram-positive bacterial infection and has recently been associated with development of adverse drug reactions, particularly following previous exposure to vancomycin. In this study, we generated teicoplanin-specific monoclonal T-cell populations from healthy volunteers expressing HLA-A*32:01 and defined pathways of T-cell activation and HLA allele restriction. Teicoplanin-responsive T-cells were CD8+, HLA class I-restricted, and cross-reacted with the lipoglycopeptide daptomycin in proliferation and cytokine/cytolytic molecule (granzyme B, Perforin, and FasL) release assays. These data show that teicoplanin activates T-cells, which may play a role in the pathogenesis of teicoplanin-induced adverse events, in HLA-A*32:01 positive donors.
DOI: 10.1093/toxsci/kfab084
发表时间: 2021-08-30
期刊: Toxicological sciences : an official journal of the Society of Toxicology
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