Application of in Vitro T Cell Assay Using Human Leukocyte Antigen-Typed Healthy Donors for the Assessment of Drug Immunogenicity

Chem Res Toxicol. 2018 Mar 19;31(3):165-167. doi: 10.1021/acs.chemrestox.8b00030. Epub 2018 Feb 14.

Abstract

It is unclear whether priming of naïve T cells to drugs is detectable in healthy human donors expressing different human leukocyte antigen (HLA) alleles. Thus, we examined T cell priming with drugs associated with HLA risk alleles and control compounds in 14 HLA-typed donors. Nitroso sulfamethoxazole and piperacillin activated T cells from all donors, whereas responses to carbamazepine and oxypurinol were only seen in donors expressing HLA-B*15:02 and HLA-B*58:01, respectively. Weak flucloxacillin-specific T cell responses were detected in donors expressing HLA-B*57:01 and HLA-B*58:01. These data show that the priming of T cells with certain drugs is skewed toward donors expressing specific HLA alleles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Infective Agents / adverse effects
  • Anti-Infective Agents / immunology
  • Anticonvulsants / adverse effects
  • Anticonvulsants / immunology
  • Carbamazepine / adverse effects
  • Carbamazepine / immunology
  • Drug-Related Side Effects and Adverse Reactions / immunology*
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / immunology
  • HLA Antigens / immunology*
  • HLA-B Antigens / immunology
  • Humans
  • Lymphocyte Activation / drug effects*
  • Nitroso Compounds / adverse effects
  • Nitroso Compounds / immunology
  • Oxypurinol / adverse effects
  • Oxypurinol / immunology
  • Piperacillin / adverse effects
  • Piperacillin / immunology
  • Sulfamethoxazole / adverse effects
  • Sulfamethoxazole / immunology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology

Substances

  • Anti-Infective Agents
  • Anticonvulsants
  • Enzyme Inhibitors
  • HLA Antigens
  • HLA-B Antigens
  • Nitroso Compounds
  • Carbamazepine
  • Oxypurinol
  • Sulfamethoxazole
  • Piperacillin