Concepts and perspectives on peptide-based immunotherapy in allergy

Allergen-specific T cells play a key role in the patho-genesis of allergic diseases through provision of help for allergen-specific B cells and control of inflammatory responses. Allergen immunotherapy using intact allergen proteins (given either sub-cutaneously or sublingually) is clinically effective and demonstrates enduring efficacy (i. e., disease modifying). However, the requirement for monthly injections or daily sublingual administration (both for 3 years), combined with a high frequency of local and systemic adverse events, results in poor compliance. Targeting allergen-specific T cells with synthetic peptides representing dominant T cell epitopes markedly decreases treatment times (4–8 intradermal injections), reduces adverse events and provides efficacy for at least 2 years. We have developed peptide immunotherapies for allergies triggered by cats, house dust mites, and grass pollen. Each of these consists of a mixture of seven peptides containing multiple dominant T cell epitopes and each have demonstrated statistically significant improvements in rhinoconjunctivitis symptom scores in controlled allergen challenge facilities. The mechanisms of action appear to involve increased IL-10 production, intra-and inter-molecu-lar suppression, and down-regulation of chemo-kine pathways. In contrast, treatment does not appear to be associated with deletion of allergen-specific T cells, nor with the induction of allergen-specific IgG (as is seen with conventional whole allergen immunotherapy).