Human TCR transgenic Bet v 1-specific Th1 cells suppress the effector function of Bet v 1-specific Th2 cells

J Immunol. 2011 Oct 15;187(8):4077-87. doi: 10.4049/jimmunol.1003220. Epub 2011 Sep 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Plant / immunology*
  • Base Sequence
  • Cell Separation
  • Cross Reactions / immunology
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Food Hypersensitivity / immunology
  • HEK293 Cells
  • Humans
  • Immunodominant Epitopes / immunology
  • Jurkat Cells
  • Lymphocyte Activation / immunology
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhinitis, Allergic, Seasonal / immunology*
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*
  • Transduction, Genetic
  • Transgenes

Substances

  • Antigens, Plant
  • Immunodominant Epitopes
  • Receptors, Antigen, T-Cell, alpha-beta
  • Bet v 1 allergen, Betula

Associated data

  • GENBANK/GQ179994
  • GENBANK/GQ179995