Epitope Mapping of Major Ragweed Allergen Amb a 1

Abida Zahirović,Mojca Lunder,Peter Korošec,Borut Štrukelj

doi:10.17344/acsi.2018.4516

Abstract

Ragweed is a prominent cause of seasonal allergies. Thus far, information on IgE-binding sites of major allergen in ragweed pollen, Amb a 1, is very limited. A powerful experimental method to gain insights on the allergen epitopes is the selection of peptides from biological libraries that bind to anti-allergen antibodies. In this work, we aimed to map IgE epitopes of Amb a 1 using epitope-mimicking short peptides - mimotopes that were affinity-selected from phage-displayed random peptide libraries. The peptides weakly aligned with the Amb a 1 primary sequence, thus suggesting that the epitopes are conformational. When the peptides were mapped onto the surface of Amb a 1 homology model, the EpiSearch analysis predicted the location of four potential epitopic sites on surface patches centred at residues K104, S110, H214, and W312. The peptides matching to the predicted epitopes bound selectively to the IgE from pool of ragweed-allergic patients' sera and therefore represent mimetics of Amb a 1 IgE epitopes. The knowledge of IgE epitopes is a prerequisite for the rational design of molecular-based approaches to diagnosis and immunotherapy of allergic diseases.

Highlights

Short ragweed (Ambrosia artemisiifolia) is one of the most important allergen source in North America.[1]
Given that the antibodies of IgG isotype were used as target, the reactivity of selected peptides with serum IgE was tested in order to evaluate whether a conserved epitope specificity between the IgG and IgE exist and to determine whether the identified peptides are mimetics of IgE epitopes in ragweed-allergic patients
Conformational mapping of the six representative peptides to the surface of the structural model of Amb a 1 predicted the location of four epitopic sites on surface patches centred at residues K104, S110, H214, and W312

Summary

Introduction

Short ragweed (Ambrosia artemisiifolia) is one of the most important allergen source in North America.[1] Because of its fast spreading, sensitization rates are increasing in Central and Southeastern Europe, ranging from 15% to ~80%.2. Current therapeutic options for ragweed allergy involve symptomatic treatment and allergen-specific immunotherapy. Conventional immunotherapy with crude pollen extracts is the only available curative treatment. It may induce undesired IgE-mediated side effects and long-term therapy is required, which often hampers patient compliance.[3,4] new approaches to immunotherapy that include well-defined therapeutic molecules with reduced or abolished IgE binding capacity are being investigated

Objectives

Results

Conclusion