Immunomodulatory Response of Toll-like Receptor Ligand-Peptide Conjugates in Food Allergy

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.

Automated summary

The covalent conjugation of allergens to toll-like receptor (TLR) agonists is a powerful strategy for developing safe compounds for allergen-specific immunomodulatory response towards tolerance in allergy. Synthesizing two families of ligands, one as a ligand for TLR7 and the other for TLR4, both conjugated with a T-cell peptide of Pru p 3 allergen, showed promising results in inducing specific maturation of dendritic cells, T-cell proliferation, and cytokine production in peach allergic patients. The increase in Treg-cell frequencies and induction of IL-10 production in patients suggest the potential application of these allergen-adjuvant systems in food allergy immunotherapy.