Abstract
Allergic sensitisation usually begins early in life. The number of allergens a patient is sensitised to can increase over time and the development of additional allergic conditions is increasingly recognised. Targeting allergic disease in childhood is thus likely to be the most efficacious means of reducing the overall burden of allergic disease. Specific immunotherapy involves administering protein allergen to tolerise allergen reactive CD4+ T cells, thought key in driving allergic responses. Yet specific immunotherapy risks allergic reactions including anaphylaxis as a consequence of preformed allergen-specific IgE antibodies binding to the protein, subsequent cross-linking and mast cell degranulation. CD4+ T cells direct their responses to short "immunodominant" peptides within the allergen. Such peptides can be given therapeutically to induce T cell tolerance without facilitating IgE cross-linking. Peptide immunotherapy (PIT) offers attractive treatment potential for allergic disease. However, PIT has not yet been shown to be effective in children. This review discusses the immunological mechanisms implicated in PIT and briefly covers outcomes from adult PIT trials. This provides a context for discussion of the challenges for the application of PIT, both generally and more specifically in relation to children.
Highlights
Allergic disease including atopic eczema, allergic rhinitis, allergic asthma and food allergy causes significant patient morbidity and economic costs to healthcare systems [1,2]
IL10 production increased from allergen-reactive T cells after Peptide immunotherapy (PIT) [36] and, in another, CD4+ T cells obtained from patients after PIT had suppressive activity in vitro [40]
Most allergens will contain multiple peptide epitopes which can vary in their ability to bind to different major histocompatibility complex II (MHC II) molecules [64], meaning that there will be differences in the allergenderived peptides which are recognised by different patients’ T cells
Summary
Allergic disease including atopic eczema, allergic rhinitis, allergic asthma and food allergy causes significant patient morbidity and economic costs to healthcare systems [1,2]. IL10 production increased from allergen-reactive T cells after PIT [36] and, in another, CD4+ T cells obtained from patients after PIT had suppressive activity in vitro [40] It appears that the development of regulatory mechanisms following PIT may be favoured by regimens using repeated peptide dosing [26], the optimal dosage and delivery regimes favouring regulation remain unclear. Most allergens will contain multiple peptide epitopes which can vary in their ability to bind to different MHC II molecules [64], meaning that there will be differences in the allergenderived peptides which are recognised by different patients’ T cells This poses difficulties for identifying immunodominant peptides capable of inducing tolerance in a HLA-diverse patient population [10].
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