From Molecule Studies of Allergens to Development of Immunotherapy of Allergies

Abstract

IntroductionAllergy is a type I hypersensitivity disease prominently influences the quality of life. Allergens can strike one through the administration of drugs, insect sting, and ingestion of food or simply inhalation, making patients hard to strictly avoid these molecules. Allergen specific immunotherapy for grass pollen allergy has been put into clinical trials since 1950s and demonstrated satisfactory therapeutic effects [1]. It therefore paves the way for extensive researches on designing different allergen specific immunotherapy and unveiling the underlying mechanisms of these therapies.Defining the immunological mechanisms leading to allergy is crucial in designing allergen-specific immunotherapy. Sensitization of allergic individuals to allergens is initialized upon presentation of the allergen-derived peptides by the antigen presenting cells (APCs) through the major histocompatibility class II molecule (MHC class II) to naïve T cells, which are then activated and differentiated into type 2 T helper cells (Th2) (Figure 1). Cytokines such as IL-4 and IL-13 from Th2 cause a class switch in B cells to produce IgE antibodies specific to the particular allergen. When the individual is exposed to the same allergen again, IgE are massively produced, cross-link with the allergen and high affinity receptor (FcεRI) on mast cells and induce degranulation. Mediators such as histamine and leukotriene are released, resulting in inflammation and other associated anaphylactic responses [2].Molecular characteristics of allergens, in particular the identification of T cell and B cell epitopes, constitute important information for the design of therapeutic regimens. T cell epitopes refer to the short peptide fragments activating Th2 via MHC class II molecules while B cell epitopes, or IgE-binding epitopes, refer to the regions recognized by IgE on the allergen. With the identification of B cell epitopes at the molecular level, hypo-allergens possessing reduced allergenicity can be constructed through the introduction of point mutations on these IgE-binding regions [3,4]. The lack of IgE reactivity reduces the risk of these hypo-allergens to form cross-links with IgE and thus prevents the development of allergic side effects during treatment [5]. Meanwhile, since the T cell epitopes are conserved, these hypo-allergens are immunogenic and thus offer therapeutic effects. Alternatively, the employment of T cell epitopes in immunotherapy is believed to be a potential strategy since small peptide fragments are incapable to form cross-link with IgE but yet immunogenic to modulate immune responses [6]. AbstractAllergies are hypersensitive reactions that affect over 25% of the world population. Extensive studies have been directed to define patho-immunological mechanisms of allergy and the molecular characteristics of allergens. The emerging B cell and T cell epitope database has greatly facilitated the development of epitope-based immunotherapy that aims at modulating patients' immune responses towards a specific allergen. Modifi...