Pharmacological interaction of drugs with antigen-specific immune receptors: the p-i concept

Abstract

Drug allergies are examples of immune reactions to small molecular compounds. In many drug allergies drug specific CD4+ and CD8+ T-cells can be detected, which recognize small chemicals via their αβ-T-cell receptor in a major histocompatibility complex dependent way. In this review a new concept of drug presentation to T-cells is presented. Drugs were stimulatory for T-cells if they bound covalently to peptides or proteins, but also if the drug had structural features allowing it to bind in a labile way (noncovalently) to the major histocompatibility peptide complex. This latter binding method has some similarities to superantigen stimulations and can explain allergies to drugs that are not metabolized. It has been described in patients with maculopapular, bullous and neutrophilic drug eruption, as well as in contact dermatitis. Noncovalent drug presentation leads to the stimulation of immune cells, namely T-cells. The drug needs two surface molecules (one inert serving as a scaffold, major histocompatibility complex, and one reactive, T-cell receptor) to exert its function. Although two receptor structures are involved, the process is reminiscent of a pharmacological interaction between a drug and its receptors and, from the phrase pharmacological interaction with immune receptors, was thus termed the p-i concept.