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

作者:Usui Toru; Faulkner Lee; Farrell John; French Neil S; Alfirevic Ana; Pirmohamed Munir; Park B Kevin; Nai**itt Dean J*
来源:Chemical Research in Toxicology, 2018, 31(3): 165-167.
DOI:10.1021/acs.chemrestox.8b00030

摘要

It is unclear whether priming of naive 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.

  • 出版日期2018-3