Pru p 3-Glycodendropeptides Based on Mannoses Promote Changes in the Immunological Properties of Dendritic and T-Cells from LTP-Allergic Patients

Abstract

Scope: Glycodendropeptides (GDPs) functionalized with mannose can enhance allergen interaction with dendritic cells (DCs) via C-type lectin receptors (CLRs), modulating the immune response. They can present multiple peptides and have potential applications for diagnosis and treatment of food allergy (FA). The immune response induced by GDPs with mannose and Pru p 3 peptides (mono/tetravalent) with ester (D₁ ManPrup3/D₄ ManPrup3) or ether linkers (D₁ Man_-O- Prup3/D₄ Man_-O- Prup3) in lipid-transfer-protein-allergic patients and tolerant controls is analyzed.

Methods and results: The immunological response induced by GDPs is studied by assessing monocyte-derived-DC maturation, lymphocyte proliferation, cytokine production, and basophil response by flow cytometry. D_n ManPrup3 was recognized by DCs via CLRs inducing DC maturation in all subjects. However, CCR7 expression is significantly upregulated in allergic patients compared to tolerant controls. These changes correlate with lymphocyte proliferation and specific production of Th2/Th1 cytokines in allergic patients. Moreover, D₁ ManPrup3 does not induce basophil activation.

Conclusion: D_n ManPrup3 induces changes in DC maturation and lymphocyte proliferation, indicating specific recognition via CLRs. Prup3-GDPs are recognized by immune cells, inducing a specific immune response and modulating the immunological response in FA patients. The specific geometry of D₁ ManPrup3 in particular makes it a potential candidate for specific immunotherapy development.

Keywords: C-type lectin receptors; dendritic cells; food allergies; lymphocytes; mannose.