PT  - JOURNAL ARTICLE
AU  - Daphné Anne Schmid
AU  - Jan Paul Heribert Depta
AU  - Michael Lüthi
AU  - Werner Joseph Pichler
TI  - 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
AID  - 10.1124/mol.105.021576
DP  - 2006 Jul 01
TA  - Molecular Pharmacology
PG  - 356--365
VI  - 70
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/70/1/356.short
4100  - http://molpharm.aspetjournals.org/content/70/1/356.full
SO  - Mol Pharmacol2006 Jul 01; 70
AB  - 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 α- and β-chains of sulfanilamide- and quinolone-specific TCR abrogated drug reactivity, suggesting that both original α- and β-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.