Covalent conjugation
of allergens to toll-like receptor (TLR) agonists
appears to be a powerful strategy for the development of safety compounds
for allergen-specific immunomodulatory response toward tolerance in
allergy. In this work, we have synthesized two family of ligands,
an 8-oxoadenine derivative as a ligand for TLR7 and a pyrimido[5,4-b]indole as a ligand for TLR4, both conjugated with a T-cell
peptide of Pru p 3 allergen, the lipid transfer protein (LTP) responsible
for LTP-dependent food allergy. These conjugates interact with dendritic
cells, inducing their specific maturation, T-cell proliferation, and
cytokine production in peach allergic patients. Moreover, they increased
the Treg-cell frequencies in these patients and could induce the IL-10
production. These outcomes were remarkable in the case of the TLR7
ligand conjugated with Pru p 3, opening the door for the potential
application of these allergen–adjuvant systems in food allergy
immunotherapy.
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