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

• Published in: ACS chemical biology 2021-11, Vol.16 (11), p.2651-2664
• Main Authors: Losada Méndez, Jorge, Palomares, Francisca, Gómez, Francisca, Ramírez-López, Pedro, Ramos-Soriano, Javier, Torres, Maria Jose, Mayorga, Cristobalina, Rojo, Javier
• Format: Article
• Language: English
• Subjects: Allergens - metabolism; Carrier Proteins - metabolism; Cell Proliferation; Cytokines - biosynthesis; Food Hypersensitivity - immunology; Food Hypersensitivity - metabolism; Humans; Immunomodulation; Ligands; Peptides - metabolism; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Toll-Like Receptor 4 - agonists; Toll-Like Receptor 4 - metabolism; Toll-Like Receptor 7 - agonists; Toll-Like Receptor 7 - metabolism
• ISSN: 1554-8929; 1554-8937
• DOI: 10.1021/acschembio.1c00765

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.