Immunotherapy with allergen peptides

Abstract

: Specific allergen immunotherapy (SIT) is disease-modifying and efficacious. However, the use of whole allergen preparations is associated with frequent allergic adverse events during treatment. Many novel approaches are being designed to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity. One approach is the use of short synthetic peptides which representing dominant T cell epitopes of the allergen. Short peptides exhibit markedly reduced capacity to cross link IgE and activate mast cells and basophils, due to lack of tertiary structure. Murine pre-clinical studies have established the feasibility of this approach and clinical studies are currently in progress in both allergic and autoimmune diseases.

Figure 1

Comparison of whole-allergen immunotherapy and peptide immunotherapy. Whole-allergen immunotherapy leads to the generation of both T helper 1 (Th1) and T regulatory (Treg) responses. Interleukin-10 (IL-10) and interferon-γ (IFN-γ) produced by T cells of treated individuals reduce eosinophil recruitment. IL-10, IFN-γ, and IL-4 drive production of allergen-specific immunoglobulin (Ig)G antibodies. Peptides are presented to T cells with costimulation leading to a mixed Th1-Treg response. Whole-allergen molecules can cross-link allergen-specific IgE on the surface of mast cells and basophils, leading to cellular activation and IgE-mediated adverse events. APC = antigen-presenting cell. In peptide immunotherapy, short peptides do not cross-link allergen-specific IgE molecules and thus mast cells and basophils are not activated. Peptides are recognized by T cells in the absence of costimulation, resulting in a predominantly regulatory response characterized by IL-10, which decreases eosinophil recruitment and mast cell activation.