Variants of allergen Phlp 5b and reduction of anaphylactogenic potential

Abstract One new approach to improved immunotherapy for type 1 allergy might be the use of modified allergens with reduced IgE reactivity but retained T cell reactivity. By site- directed mutagenesis outside the dominant T cell epitopes, we generated deletion mutants of the grass pollen allergen Phl p 5b. Some of these variants revealed significantly reduced IgE reactivity and histamine releasing capacity compared to the wild-type allergen. Furthermore, in vivo skin prick tests showed that the variants had up to 100 fold lower potency to induce cutaneous reactions than the wild-type allergen. On the other hand, T cell clones and T cell lines from grass pollen-allergic patients showed comparable proliferation after stimulation with these variants and wild-type allergen. Thus, variants of the allergen Phl p 5b with reduced anaphylactogenic potential but retained T cell reactivity could be valuable tools for improved allergen-specific immunotherapy.