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The MHC class II-restricted CD4+ T-cell receptor (TCR) recognizing grass pollen-derived peptides is a critical mediator of allergic sensitization and chronic inflammation in seasonal allergic rhinitis (Wambre et al., 2012, Science Translational Medicine). These receptors are expressed on CD4+ T cells and specifically recognize epitopes from major grass allergens, such as Phl p 1 and Phl p 5, when presented by MHC class II molecules (HLA-DR/DQ/DP) on antigen-presenting cells (Würtzen et al., 2007, Clinical & Experimental Allergy). Upon binding, the TCR triggers a signaling cascade that promotes a Th2-polarized immune response, leading to the production of allergen-specific IgE and the recruitment of eosinophils and mast cells (Larche et al., 2006, Nature Reviews Immunology). This TCR complex is the primary target for allergen-specific immunotherapy (AIT), including sublingual (SLIT) and subcutaneous (SCIT) treatments like Grazax or Oralair (Jutel et al., 2015, Journal of Allergy and Clinical Immunology). Therapeutic intervention aims to induce peripheral T-cell tolerance, characterized by the induction of regulatory T cells (Tregs) and a shift toward IgG4 production, thereby dampening the allergic cascade upon subsequent pollen exposure.
Allergen-specific immunotherapy (AIT) targets these TCRs to induce immunological tolerance. This is achieved through the induction of T-cell anergy, clonal deletion, or the differentiation of IL-10-secreting regulatory T cells (Tregs), which suppress the Th2-driven allergic response (Jutel et al., 2015, Journal of Allergy and Clinical Immunology).
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