title: Human TCR transgenic Bet v 1-specific Th1 cells suppress the effector function of Bet v 1-specific Th2 cells.
abstract: Pollinosis to birch pollen is a common type I allergy in the Northern Hemisphere. Moreover, birch pollen-allergic individuals sensitized to the major birch pollen allergen Bet v 1 frequently develop allergic reactions to stone fruits, hazelnuts, and certain vegetables due to immunological cross-reactivity. The major T cell epitope Bet v 1(142-153) plays an important role in cross-reactivity between the respiratory allergen Bet v 1 and its homologous food allergens. In this study, we cloned and functionally analyzed a human αβ TCR specific for the immunodominant epitope Bet v 1(142-153). cDNAs encoding TCR α- and β-chains were amplified from a Bet v 1(142-153)-specific T cell clone, introduced into Jurkat T cells and peripheral blood T lymphocytes of allergic and nonallergic individuals, and evaluated functionally. The resulting TCR transgenic (TCRtg) T cells responded in an allergen-specific and costimulation-dependent manner to APCs either pulsed with Bet v 1(142-153) peptide or coexpressing invariant chain::Bet v 1(142-153) fusion proteins. TCRtg T cells responded to Bet v 1-related food and tree pollen allergens that were processed and presented by monocyte-derived dendritic cells. Bet v 1(142-153)-presenting but not Bet v 1(4-15)-presenting artificial APCs coexpressing membrane-bound IL-12 polarized allergen-specific TCRtg T cells toward a Th1 phenotype, producing high levels of IFN-γ. Coculture of such Th1-polarized T cells with allergen-specific Th2-differentiated T cells significantly suppressed Th2 effector cytokine production. These data suggest that human allergen-specific TCR can transfer the fine specificity of the original T cell clone to heterologous T cells, which in turn can be instructed to modulate the effector function of the disease initiating/perpetuating allergen-specific Th2-differentiated T cells.
authors: Christian Doppler Laboratory for Immunomodulation, Vienna A-1090, Austria.
authors: Alina
authors: A
authors: Neunkirchner
authors: Victoria M
authors: VM
authors: Leb-Reichl
authors: Klaus G
authors: KG
authors: Schmetterer
authors: Sonja
authors: S
authors: Mutschlechner
authors: Hans J
authors: HJ
authors: Kueng
authors: Daniela
authors: D
authors: Haiderer
authors: Karina
authors: K
authors: Schuch
authors: Michael
authors: M
authors: Wallner
authors: Beatrice
authors: B
authors: Jahn-Schmid
authors: Barbara
authors: B
authors: Bohle
authors: Winfried F
authors: WF
authors: Pickl
mesh_terms: D000595:Amino Acid Sequence; D052179:Antigens, Plant / Q000276:immunology*; D001483:Base Sequence; D002469:Cell Separation; D003429:Cross Reactions / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005512:Food Hypersensitivity / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014161:Transduction, Genetic; D019076:Transgenes
chemical_list: D052179:Antigens, Plant; D016056:Immunodominant Epitopes; D016693:Receptors, Antigen, T-Cell, alpha-beta; C061312:Bet v 1 allergen, Betula