title: Immunoregulatory T cell epitope peptides: the new frontier in allergy therapy.
abstract: 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.
authors.affiliation: Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Vic., Australia.|Department of Immunology, Monash University, Melbourne, Vic., Australia.
authors.forename: S R
authors.initials: SR
authors.lastname: Prickett
authors.affiliation: Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Vic., Australia.|Department of Immunology, Monash University, Melbourne, Vic., Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Rolland
authors.affiliation: Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Central Clinical School, Monash University, Melbourne, Vic., Australia.|Department of Immunology, Monash University, Melbourne, Vic., Australia.
authors.forename: R E
authors.initials: RE
authors.lastname: O'Hehir
mesh_terms: D000485:Allergens / Q000737:chemistry / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D018604:Epitope Mapping / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy; D007155:Immunologic Factors / Q000627:therapeutic use; D056747:Immunomodulation; D007167:Immunotherapy; D058990:Molecular Targeted Therapy; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D057170:Translational Research, Biomedical; D016896:Treatment Outcome
chemical_list: D000485:Allergens; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D007155:Immunologic Factors; D010455:Peptides