MRC Center for Drug Safety Science, Department of Molecular and Clinical Pharmacology , University of Liverpool , Sherrington Building, Ashton Street , Liverpool , L69 3GE , England.
Institute of Cellular Medicine, Medical School , Newcastle University , Newcastle NE2 4HH , United Kingdom.
Chem Res Toxicol. 2018 Oct 15;31(10):1022-1024. doi: 10.1021/acs.chemrestox.8b00163. Epub 2018 Sep 13.
The HLA class I allele HLA-A33:03 is a risk factor for ticlopidine-induced liver injury. Herein, we show HLA class I-restricted ticlopidine-specific CD8+ T-cell activation in healthy donors expressing HLA-A33:03. Cloned CD8+ T-cells proliferated and secreted IFN-γ in the presence of ticlopidine and autologous antigen presenting cells. A reduction of the T-cell response after blocking with HLA-class I and HLA-A*33 antibodies indicates that the interaction between drugs and the HLA allele detected in genetic association studies may be important for T-cell activation.
HLA Ⅰ类等位基因 HLA-A33:03 是噻氯匹定诱导肝损伤的危险因素。在此，我们显示了在表达 HLA-A33:03 的健康供体中 HLA Ⅰ类限制的噻氯匹定特异性 CD8+T 细胞的激活。在噻氯匹定和自体抗原呈递细胞存在的情况下，克隆的 CD8+T 细胞增殖并分泌 IFN-γ。用 HLA Ⅰ类和 HLA-A*33 抗体阻断后 T 细胞反应减少，表明遗传关联研究中检测到的药物与 HLA 等位基因之间的相互作用可能对 T 细胞激活很重要。
