Dissection of immunoglobulin E and T lymphocyte reactivity of isoforms of the major birch pollen allergen Bet v 1: potential use of hypoallergenic isoforms for immunotherapy

J Exp Med. 1996 Feb 1;183(2):599-609. doi: 10.1084/jem.183.2.599.


We dissected the T cell activation potency and the immunoglobulin (Ig) E-binding properties (allergenicity) of nine isoforms of Bet v 1 (Bet v 1a-Bet v 1l), the major birch pollen allergen. Immunoblot experiments showed that Bet v 1 isoforms differ in their ability to bind IgE from birch pollen-allergic patients. All patients tested displayed similar IgE-binding patterns toward each particular isoform. Based on these experiments, we grouped Bet v 1 isoforms in three classes: molecules with high IgE-binding activity (isoforms a, e, and j), intermediate IgE-binding (isoforms b, c, and f), and low/no IgE-binding activity (isoforms d, g, and 1). Bet v 1a, a recombinant isoform selected from a cDNA expression library using IgE immunoscreening exhibited the highest IgE-binding activity. Isoforms a, b, d, e, and 1 were chosen as representatives from the three classes for experimentation. The potency of each isoallergen to activate T lymphocytes from birch pollen-allergic patients was assayed using peripheral blood mononuclear cells, allergen-specific T cell lines, and peptide-mapped allergen-specific T cell clones. Among the patients, some displayed a broad range of T cell-recognition patterns for Bet v 1 isoforms whereas others seemed to be restricted to particular isoforms. In spite of this variability, the highest scores for T cell proliferative responses were observed with isoform d (low IgE binder), followed by b, 1, e, and a. In vivo (skin prick) tests showed that the potency of isoforms d and 1 to induce typical urticarial type 1 reactions in Bet v 1-allergic individuals was significantly lower than for isoforms a, b, and e. Taken together, our results indicate that hypoallergenic Bet v 1 isoforms are potent activators of allergen-specific T lymphocytes, and Bet v 1 isoforms with high in vitro IgE-binding activity and in vivo allergenicity can display low T cell antigenicity. Based on these findings, we propose a novel approach for immunotherapy of type I allergies: a treatment with high doses of hypoallergenic isoforms or recombinant variants of atopic allergens. We proceed on the assumption that this measure would modulate the quality of the T helper cell response to allergens in vivo. The therapy form would additionally implicate a reduced risk of anaphylactic side effects.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / chemistry
  • Allergens / immunology*
  • Allergens / therapeutic use
  • Amino Acid Sequence
  • Antigens, Plant
  • Base Sequence
  • Clone Cells
  • Cloning, Molecular
  • Electrophoresis, Polyacrylamide Gel
  • Epitopes
  • Humans
  • Hypersensitivity / therapy*
  • Immunoblotting
  • Immunotherapy / methods
  • Molecular Sequence Data
  • Plant Proteins / chemistry
  • Plant Proteins / genetics
  • Plant Proteins / immunology*
  • Plant Proteins / therapeutic use
  • Pollen / chemistry
  • Pollen / immunology*
  • Recombinant Proteins / immunology
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / therapeutic use
  • Sequence Analysis
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • T-Lymphocytes / immunology*


  • Allergens
  • Antigens, Plant
  • Epitopes
  • Plant Proteins
  • Recombinant Proteins
  • Bet v 1 allergen, Betula