Epitope peptides and immunotherapy.
Allergic diseases affect atopic individuals, who synthesize specific Immunoglobulins E (IgE) to environmental allergens, usually proteins or glycoproteins. These allergens include grass and tree pollens, indoor allergens such as house dust mites and animal dander, and various foods. Because allergen-specific IgE antibodies are the main effector molecules in the immune response to allergens, many studies have focused on the identification of IgE-binding epitopes (called B cell epitopes), specific and minimum regions of allergen molecules that binds to IgE. Our initial studies have provided evidence that only four to five amino acid residues are enough to comprise an epitope, since pentapeptide QQQPP in wheat glutenin is minimally required for IgE binding. Afterwards, various kinds of B cell epitope structures have been clarified. Such information contributes greatly not only to the elucidation of the etiology of allergy, but also to the development of strategies for the treatment and prevention of allergy. Allergen-specific T cells also play an important role in allergy and are obvious targets for intervention in the disease. Currently, the principle approach is to modify B cell epitopes to prevent IgE binding while preserving T cell epitopes to retain the capacity for immunotherapy. There is mounting evidence that the administration of peptide(s) containing immunodominant T cell epitopes from an allergen can induce T cell nonresponsiveness (immunotherapy). There have been clinical studies of peptide immunotherapy performed, the most promising being for bee venom sensitivity. Clinical trials of immunotherapy for cat allergen peptide have also received attention. An alternative strategy for the generation of an effective but hypoallergenic preparation for immunotherapy is to modify T cell epitope peptides by, for example, single amino acid substitution. In this article, I will present an overview of epitopes related to allergic disease, particularly stress on allergen specific immunotherapy. In addition, our ongoing study of immunotherapy by 'eating' T cell epitope peptides will be described. Eating T cell epitope peptides as food provides a more practical way of inducing tolerance and a challenge to prevent allergy in daily life, as opposed to therapy by ingesting peptides as medicine.
Tanabe
Soichi
S
Hiroshima University, 1-4-4, Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8528, Japan. stanabe@hiroshima-u.ac.jp
D000284:Administration, Oral; D000485:Allergens / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001516:Bees; D002415:Cats; D000939:Epitopes / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000628:therapy; D007073:Immunoglobulin E / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods*; D007299:Insect Bites and Stings / Q000276:immunology; D018448:Models, Immunological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology
D000485:Allergens; D000939:Epitopes; D010455:Peptides; D007073:Immunoglobulin E