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Transfection of Drug-Specific T-Cell Receptors into Hybridoma Cells: Tools to Monitor Drug Interaction with T-Cell Receptors and Evaluate Cross-Reactivity to Related Compounds

Division of Allergology, Inselspital, University of Bern, Bern, Switzerland

In the context of drug hypersensitivity, our group has recently proposed a new model based on the structural features of drugs (pharmacological interaction with immune receptors; p-i concept) to explain their recognition by T cells. According to this concept, even chemically inert drugs can stimulate T cells because certain drugs interact in a direct way with T-cell receptors (TCR) and possibly major histocompatibility complex molecules without the need for metabolism and covalent binding to a carrier. In this study, we investigated whether mouse T-cell hybridomas transfected with drug-specific human TCR can be used as an alternative to drug-specific T-cell clones (TCC). Indeed, they behaved like TCC and, in accordance with the p-i concept, the TCR recognize their specific drugs in a direct, processing-independent, and dose-dependent way. The presence of antigen-presenting cells was a prerequisite for interleukin-2 production by the TCR-transfected cells. The analysis of cross-reactivity confirmed the fine specificity of the TCR and also showed that TCR transfectants might provide a tool to evaluate the potential of new drugs to cause hypersensitivity due to cross-reactivity. Recombining the - and -chains of sulfanilamide- and quinolone-specific TCR abrogated drug reactivity, suggesting that both original - and -chains were involved in drug binding. The TCR-transfected hybridoma system showed that the recognition of two important classes of drugs (sulfanilamides and quinolones) by TCR occured according to the p-i concept and provides an interesting tool to study drug-TCR interactions and their biological consequences and to evaluate the cross-reactivity potential of new drugs of the same class.

Address correspondence to: Prof. Werner J. Pichler, MD/Division of Allergology, Inselspital, University of Bern, 3010 Bern, Switzerland. E-mail: werner.pichler{at}insel.ch

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