Sequences of peptide mimotopes (A) and their attachment to the primary and tertiary structure of Api m 1 (B and C).Binding of the allergen and peptide mimotopes to IgE from patient serums (D).
Image source: Zahirović A., Koren A., Kopač P., Štrukelj B., Korošec P., Lunder M. Identification of bee venom Api m 1 IgE epitopes and characterization of corresponding mimotopes. J Allergy Clin Immunol., 143 (2019), 791-794.
Publish Date: 19.12.2019
Category: Outstanding research achievements, Interdisciplinary research, Our contribution to sustainable development goals
Sustainable development goals: 3 Good health and well-being (Indicators)
Researchers from the University of Ljubljana, Faculty of Pharmacy (Abida Zahirović, Borut Štrukelj, Mojca Lunder) and the University Clinic of Respiratory and Allergic Diseases Golnik (Ana Koren, Peter Kopač, Peter Korošec) identified thus far unknown IgE-epitopes of the main bee venom allergen Api m 1 and evaluated the immunotherapeutic potential of the peptides that mimic these epitopes (mimotopes).
Authors: Abida Zahirović, Borut Štrukelj, Mojca Lunder, Ana Koren, Peter Kopač, Peter Korošec
The conventional immunotherapy for allergy to bee venom is associated with frequent side effects, including systemic reactions. For development of safer immunotherapy peptide mimotopes show great potential. As small molecules they do not cross-link IgE antibodies on patients’ effector cells, and in combination with an appropriate immunogenic carrier they are also capable of stimulating a T-cell response. The researchers obtained peptide mimetics by screening libraries of random peptides and by computational mapping to three-dimensional structure of allergen identified the location of dominant epitopes. The peptide mimotopes were expressed as fusions with the bacteriophage protein pIII and their interaction with IgE from bee venom allergic patient sera was confirmed. Synthetic peptides showed no activation of patients’ basophils i.e. they have no allergogenic activity. By measuring the secretion of cytokines they confirmed that the peptides do not promote a T-cell response. While the bee venom and Api m 1 stimulated mainly Th2 response, the effect of the peptide mimotopes on the formation of cytokines was negligible. However, combined with the carrier pIII the peptides induced the secretion of IFN-γ, which indicates a prefered shift in the immune response from Th2 to Th1.
Identification of the IgE epitopes of Api m 1 and their corresponding mimotopes represents a major progress in understanding the pathogenesis of anaphylactic reaction triggered by bee venom, and opens up the possibility of developing alternative, safer and more targeted immunotherapy. The results are published in a leading allergological journal with an impact factor of 14.11.
Source: Zahirović A., Koren A., Kopač P., Štrukelj B., Korošec P., Lunder M. Identification of bee venom Api m 1 IgE epitopes and characterization of corresponding mimotopes. J Allergy Clin Immunol., 143 (2019), 791-794.
Zahirović A., Luzar J., Molek P., Kruljec N., Lunder M. Bee venom immunotherapy: current status and future directions. Clin Rev Allergy Immunol. (2019), doi: 10.1007/s12016-019-08752-x.