Research Article | Open Access
Amino Acid Substitution in Par j 2 Recombinant Allergen and Its Effect on IgE Binding Capacity
Therapeutic attempts to cure allergic diseases reduce symptoms without circumventing the onset of the allergic reaction. Specific immunotherapy (SIT), is the most commonly used treatment. Nevertheless, SIT may account for various adverse events. Therefore, different therapies have been developed in order to treat and prevent allergic reactions. Among these therapies, there is an increased interest in studying recombinant peptides mutated in the IgE binding site. Several studies have shown two major allergens of Parietaria judaica (Pj) named Par j 1 and Par j 2, which have been cloned and characterized by us. In our study we have fragmented the Par j 2 protein in order to determine the major epitopes recognized by human IgE and we used site-directed mutagenesis to identify potential amino acid residues involved in IgE binding. The IgE binding activity of the recombinant peptides was tested and the results showed that site-specific mutagenesis at positions K41, T42, T43, and C52 caused a loss of IgE binding. The goal of this work is to synthesize molecules which can induce a protective immune response against Pj. These molecules will be used in immunotherapy in order to create new vaccines for the treatment of Parietaria pollen allergy.
- A. K. Abbas, A. H. Lichtman, and J. S. Pober, Cellular and Molecular Immunology, W.B. Saunders, Philadelphia, Pa, USA, 2000.
- W. Burks, G. Bannon, and S. B. Lehrer, “Classic specific immunotherapy and new perspectives in specific immunotherapy for food allergy,” Allergy, vol. 56, no. 67, pp. 121–124, 2001.
- A. Amoresano, P. Pucci, G. Duro et al., “Assignment of disulphide bridges in Par j 2.0101, a major allergen of Parietaria judaica pollen,” Biological Chemistry, vol. 384, no. 8, pp. 1165–1172, 2003.
- P. Colombo, D. Kennedy, T. Ramsdale et al., “Identification of an immunodominant IgE epitope of the Parietaria judaica major allergen,” The Journal of Immunology, vol. 160, no. 6, pp. 2780–2785, 1998.
- M. A. Costa, P. Colombo, V. Izzo et al., “cDNA cloning, expression and primary structure of Par j I a major allergen of Parietaria judaica pollen,” FEBS Letters, vol. 341, no. 2-3, pp. 182–186, 1994.
- M. A. Costa, G. Duro, V. Izzo et al., “The IgE-binding epitopes of rPar j 2, a major allergen of Parietaria judaica pollen, are heterogeneously recognized among allergic subjects,” Allergy, vol. 55, no. 3, pp. 246–250, 2000.
- G. Duro, P. Colombo, M. A. Costa et al., “Isolation and characterization of two cDNA clones coding for isoforms of the Parietaria judaica major allergen Par j 1.0101,” International Archives of Allergy and Immunology, vol. 112, no. 4, pp. 348–355, 1997.
- G. Duro, P. Colombo, M. A. Costa et al., “cDNA cloning, sequence analysis and allergological characterization of Par j 2.0101, a new major allergen of the Parietaria judaica pollen,” FEBS Letters, vol. 399, no. 3, pp. 295–298, 1996.
- E. Pace, G. Duro, S. La Grutta et al., “Hypoallergenic fragment of Par j 2 increases functional expression of Toll-like receptors in atopic children,” Allergy, vol. 61, no. 12, pp. 1459–1466, 2006.
- M. Masullo, S. Mariotta, L. Torrelli, E. Graziani, S. Anticoli, and F. Mannino, “Respiratory allergy to Parietaria pollen in 348 subjects,” Allergologia et Immunopathologia, vol. 24, no. 1, pp. 3–6, 1996.
- B. Wuthrich, “Epidemiology of allergic diseases: are they really on the increase?,” International Archives of Allergy and Immunology, vol. 90, pp. 3–10, 1989.
- F. Ferreira, P. Briza, D. Inführ et al., “Modified recombinant allergens for safer immunotherapy,” Inflammation & Allergy Drug Targets, vol. 5, no. 1, pp. 5–14, 2006.
- J. N. Francis and M. Larché, “Peptide-based vaccination: where do we stand?,” Current Opinion in Allergy and Clinical Immunology, vol. 5, no. 6, pp. 537–543, 2005.
- M. Larché, C. A. Akadis, and R. Valenta, “Immunological mechanisms of allergen-specific immunotherapy,” Nature Reviews Immunology, vol. 6, no. 10, pp. 716–771, 2006.
- J. Rolland and R. O'Hehir, “Immunotherapy of allergy: anergy, deletion, and immune deviation,” Current Opinion in Immunology, vol. 10, no. 6, pp. 640–645, 1998.
- K. Takabayashi, L. Libet, D. Chisholm, J. Zubeldia, and A. A. Horner, “Intranasal immunotherapy is more effective than intradermal immunotherapy for the induction of airway allergen tolerance in Th2-sensitized mice,” The Journal of Immunology, vol. 170, no. 7, pp. 3898–3905, 2003.
- Y. Ma, G. Gadermaier, B. Bohle et al., “Mutational analysis of amino acid positions crucial for IgE-binding epitopes of the major apple (Malus domestica) allergen, Mal d 1,” International Archives of Allergy and Immunology, vol. 139, no. 1, pp. 53–62, 2005.
Copyright © 2009 Domenico Nuzzo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.