Received for publication December 8, 2005.
Revised March 2, 2006.
Accepted for publication April 14, 2006.

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

Abstract

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 since certain drugs interact in a direct way with T cell receptors (TCR) and possibly major histo-compatibility complex molecules without the need for metabolism and covalent binding to a carrier. Here we investigate 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 behave like TCC and in accordance with the p-i concept: the TCR recognize their specific drug 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 are involved in drug binding. The TCR-transfected hybridoma system shows that the recognition of two important classes of drugs (sulfanilamides and quinolones) by TCR occurs according to the p-i concept and provides an interesting tool to study drug-TCR interactions and their biological consequences, and evaluate the cross-reactivity potential of new drugs of the same class.

Key words: Fluorescence techniques, Receptor binding studies, Receptor-mediated

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