Allergen immunotherapy (AIT) has been practised since 1911 and remains the only
therapy proven to modify the natural history of allergic diseases. Although efficacious in carefully selected individuals, the currently licensed whole
allergen extracts retain the risk of
IgE-mediated adverse events, including
anaphylaxis and occasionally death. This together with the need for prolonged treatment regimens results in poor patient adherence. The central role of the T cell in orchestrating the immune response to
allergen informs the choice of T cell targeted
therapies for down-regulation of aberrant allergic responses. Carefully mapped short synthetic
peptides that contain the dominant
T cell epitopes of major
allergens and bind to a diverse array of HLA class II alleles, can be delivered intradermally into non-inflamed skin to induce sustained clinical and immunological tolerance. The short
peptides from allergenic
proteins are unable to cross-link
IgE and possess minimal inflammatory potential. Systematic progress has been made from in vitro human models of
allergen T cell epitope-based
peptide anergy in the early 1990s, through proof-of-concept murine
allergy models and early human trials with longer
peptides, to the current randomized, double-blind, placebo-controlled clinical trials with the potential new class of synthetic short immune-regulatory T cell
epitope peptide therapies. Sustained efficacy with few adverse events is being reported for cat, house dust mite and grass
pollen allergy after only a short course of treatment. Underlying immunological mechanisms remain to be fully delineated but anergy, deletion, immune deviation and Treg induction all seem contributory to successful outcomes, with changes in
IgG4 apparently less important compared to conventional AIT.
T cell epitope peptide therapy is promising a safe and effective new class of specific treatment for
allergy, enabling wider application even for more severe allergic diseases.