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-positive cells should result in the suppression of IgE production, thereby alleviating the symptoms of IgE-mediated allergy. In this study, we examined, in a model system, whether IgE-specific effector T cells can be used specifically to eradicate IgE-producing B cells. To this end, 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 configurations of chimeric receptor were used: in the first, we combined the heavy and light variable region chains of 84.1c with the constant (C) regions of the TCR alpha and beta chains. The second construct consisted of a chimeric single-chain receptor (scFvR), composed of a single-chain Fv region of the 84.1c antibody and the C beta domain of the TCR. Following transfection of the cTCR or the scFvR genes into the murine 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 cells. Moreover, cytotoxic T cell hybridomas expressing the chimeric receptor genes specifically eliminated IgE-secreting B cells in vitro, resulting in isotype-specific suppression of IgE production.
Lustgarten
J
J
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Eshhar
Z
Z
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000235:genetics* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D017637:Clonal Deletion; D006224:Cricetinae; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000517:prevention & control; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007128:Immunoglobulin Fragments / Q000235:genetics* / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007376:Interleukin-2 / Q000276:immunology; D015847:Interleukin-4 / Q000494:pharmacology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D007376:Interleukin-2; D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; C026408:anti-IgE antibodies; C055966:immunoglobulin Fv; D015847:Interleukin-4; D007073:Immunoglobulin E