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

Schmid, Daphné Anne; Depta, Jan Paul Heribert; Lüthi, Michael; Pichler, Werner Joseph (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. Molecular pharmacology, 70(1), pp. 356-65. Bethesda, Md.: American Society for Pharmacology and Experimental Therapeutics 10.1124/mol.105.021576

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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 alpha- and beta-chains of sulfanilamide- and quinolone-specific TCR abrogated drug reactivity, suggesting that both original alpha- and beta-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 occurred 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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology and Immunology
UniBE Contributor:	Pichler, Werner Joseph
ISSN:	0026-895X
ISBN:	16617162
Publisher:	American Society for Pharmacology and Experimental Therapeutics
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:46
Last Modified:	05 Dec 2022 14:14
Publisher DOI:	10.1124/mol.105.021576
PubMed ID:	16617162
Web of Science ID:	000238438100039
URI:	https://boris.unibe.ch/id/eprint/19092 (FactScience: 1461)