House dust mite-specific CD4+ T-cell receptor (HDM-specific TCR)

House dust mite-specific CD4+ T-cell receptors (TCRs) are specialized heterodimeric proteins expressed on the surface of CD4+ T lymphocytes that recognize peptides derived from house dust mite (HDM) allergens, such as Der p 1 and Der p 2, presented by Major Histocompatibility Complex (MHC) class II molecules (Cousin et al., 2021, Journal of Allergy and Clinical Immunology). These receptors are pivotal in the development and maintenance of allergic sensitization, as their activation by HDM allergens triggers a Th2-polarized immune response (Wambre et al., 2017, Science Translational Medicine). Upon engagement with the MHC-peptide complex, these TCRs initiate signaling cascades that lead to the secretion of pro-inflammatory cytokines like IL-4, IL-5, and IL-13 (Seumois et al., 2016, Nature Communications). This process promotes B-cell class switching to IgE and the recruitment of eosinophils, which are hallmarks of chronic airway inflammation in allergic asthma and rhinitis. Therapeutically, these TCRs are the primary targets of allergen-specific immunotherapy (AIT), which aims to induce immunological tolerance by promoting T-cell anergy or the differentiation of HDM-specific regulatory T-cells (Tregs) (Larché, 2007, Nature Reviews Immunology). Emerging strategies include the use of synthetic peptide immuno-regulatory epitopes (SPIREs) designed to target these TCRs without cross-linking IgE on mast cells, thereby reducing the risk of anaphylaxis (Baxi et al., 2020, Journal of Allergy and Clinical Immunology).

Other names

House dust mite-reactive T-cell receptorDermatophagoides pteronyssinus-specific TCRHDM-specific CD4+ TCRAllergen-specific T-cell receptor

Induction of immune tolerance through T-cell anergy, deletion of pathogenic Th2 clones, or expansion of regulatory T-cells (Tregs) following repeated exposure to specific MHC-peptide complexes (Larché, 2007, Nature Reviews Immunology).