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Introduction: Adverse drug reactions with an immune pathogenesis are a problem in the clinic and an impediment to drug development. T lymphocytes are believed to play a role in the pathogenesis; however, the nature of the drug interaction with immune receptors remains an area of debate.

Areas covered: This article reviews recent advances in our understanding of drug hypersensitivity focusing specifically on the way in which drugs are displayed in MHC molecules. Most drugs associated with a high incidence of reactions have been shown to form protein-reactive metabolites. Hence, the relationship between drug metabolism and T-cell activation is discussed in detail.

Expert opinion: The role of metabolism in pathogenesis of immunological drug reactions has only been studied with a small number of drugs where synthetic metabolites are available for functional studies. In each case, metabolite-responsive T …