HLA-A*33:03-Restricted Activation of Ticlopidine-Specific T-Cells from Human Donors

Chem Res Toxicol. 2018 Oct 15;31(10):1022-1024. doi: 10.1021/acs.chemrestox.8b00163. Epub 2018 Sep 13.

Abstract

The HLA class I allele HLA-A*33:03 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-A*33:03. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation / drug effects
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Genotype
  • HLA-A Antigens / genetics
  • HLA-A Antigens / metabolism*
  • Humans
  • Interferon-gamma / metabolism
  • Lymphocyte Activation / drug effects*
  • Ticlopidine / toxicity*

Substances

  • HLA-A Antigens
  • HLA-A*33 antigen
  • Interferon-gamma
  • Ticlopidine