Allergen-derived peptide–Major Histocompatibility Complex class II complex (Allergen-pMHCII)

The allergen-derived peptide–Major Histocompatibility Complex class II (pMHCII) complex is a molecular assembly formed when an allergen protein is processed by antigen-presenting cells (APCs) into short peptide fragments and loaded onto MHC class II molecules, such as HLA-DR, DQ, or DP [Sabatos-Peylett, M., et al., Current Opinion in Immunology, 2010]. This complex is displayed on the APC surface and is specifically recognized by the T-cell receptor (TCR) of CD4+ T cells, a critical step in the initiation and maintenance of the allergic immune response. In sensitized individuals, this recognition typically activates Th2 cells, which secrete cytokines like IL-4, IL-5, and IL-13, driving IgE production and eosinophilic inflammation [Wambre, E., et al., Science Translational Medicine, 2017]. Therapeutic strategies such as allergen immunotherapy (AIT) and peptide-based vaccines target this complex to modify the T-cell response, aiming to induce immune tolerance through mechanisms like T-cell anergy, deletion of pathogenic Th2 cells, or the induction of regulatory T cells (Tregs) [Larche, M., Nature Reviews Immunology, 2007]. By focusing on the pMHCII-TCR axis, these therapies attempt to provide long-term disease modification rather than just symptomatic relief. Peptide-based approaches are particularly designed to bind MHC II without cross-linking IgE on mast cells, thereby reducing the risk of anaphylaxis during treatment [Durham, S. R., & Shamji, M. H., Nature Reviews Immunology, 2023].

Other names

Allergen-peptide-MHC II complexpMHCII complexAllergen-MHC II complexAntigen-MHC class II complexPeptide-MHC class II complex

Induction of T-cell anergy, deletion of allergen-specific Th2 cells, and promotion of regulatory T cell (Treg) differentiation through specific TCR-pMHCII interaction [Larche, M., Nature Reviews Immunology, 2007].