SPECIFIC ELIMINATION OF IGE PRODUCTION USING T-CELL LINES EXPRESSING CHIMERIC T-CELL RECEPTOR GENES

B cells that are destined to secrete IgE express a membrane-bound form of IgE (mIgE) on their cell surface. Thus, elimination of such mIgE-p ositive cells should result in the suppression of IgE production, ther eby alleviating the symptoms of IgE-mediated allergy. In this study, w e examined, in a model system, whether IgE-specific effector T cells c an be used specifically to eradicate IgE-producing B cells. To this en d, we endowed T cells with anti-IgE specificity using chimeric T cell receptors (cTCR) containing the variable region domain (Fv) of the 84. 1c non-anaphylactic anti-mouse IgE monoclonal antibody (mAb). Two conf igurations of chimeric receptor were used: in the first, we combined t he heavy and light variable region chains of 84.1c with the constant ( C) regions of the TCR alpha and beta chains. The second construct cons isted of a chimeric single-chain receptor (scFvR), composed of a singl e-chain Fv region of the 84.1c antibody and the C beta domain of the T CR. Following transfection of the cTCR or the scFvR genes into the mur ine MD.45 cytotoxic T cell hybridoma or the Jurkat human T cell line, functional expression of IgE-specific chimeric receptors was detected on the cell surface. The transfected cells secreted interleukin-2 upon stimulation with immobilized IgE or fixed IgE-producing hybridoma cel ls. Moreover, cytotoxic T cell hybridomas expressing the chimeric rece ptor genes specifically eliminated IgE-secreting B cells in vitro, res ulting in isotype-specific suppression of IgE production.