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

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 11), the major birch pollen allergen. Immunoblot experimen ts showed that Bet v 1 isoforms differ in their ability to bind ISE fr om birch pollen-allergic patients. All patients tested displayed simil ar 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 Ig E-binding (isoforms b, c, and f), and low/no IgE-binding activity (iso forms d, g, and 1). Bet v 1a, a recombinant isoform selected from a cD NA expression library using IgE immunoscreening, exhibited the highest IgE-binding activity. Isoforms a, b, d, e, and 1 were chosen as repre sentatives 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, allerge n-specific T cell lines, and peptide-mapped allergen-specific T cell c lones. Among the patients, some displayed a broad range of T cell-reco gnition patterns for Bet v 1 isoforms whereas others seemed to be rest ricted to particular isoforms. In spite of this variability, the highe st scores for T cell proliferative responses were observed with isofor m 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 u rticarial type I reactions in Bet v 1-allergic individuals was signifi cantly lower than for isoforms a, b, and e. Taken together, our result s 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 approa ch 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 qu ality of the T helper cell response to allergens in vivo. The therapy form would additionally implicate a reduced risk of anaphylactic side effects.