Recombinant Allergens and Applications

  • Ying-Tao Ma
  • Zhao-Wei Yang
  • Zhong-Shan Gao
Part of the Advanced Topics in Science and Technology in China book series (ATSTC)

Abstract

Recombinant DNA technology has great potential in various aspects of allergen-related research and clinical applications. Sufficient amounts of purified wild-type or immunologically modified allergens or fragments have been produced in heterologous expression systems for use in many research fields, such as molecular characterization of the allergen (e.g., three-dimensional structure and epitope mapping), allergen standardization, component-resolved diagnosis (CRD) and patient-tailored specific immunotherapy (SIT). Strategies for obtaining recombinant allergens generally involve three steps, with the choice of heterologous expression system, bacteria, yeast, insect or plant cell, and the purification methods being of major importance. Here we review the major methods used for determining the three-dimensional structure and for epitope mapping, the recent progress in the application of recombinant allergens in clinical research of allergenic disease, such as the recombinant allergen-based microarray diagnosis and therapeutic vaccine.

Keywords

Recombinant Allergen Natural Counter Recombinant Aller 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Ahrazem, O., Ibanez, M.D., Lopez-Torrejon, G., et al. (2005). Lipid transfer proteins and allergy to oranges. Int Arch Allergy Immunol, 137(3), 201–210.PubMedCrossRefGoogle Scholar
  2. Arnon, R., Vanregenmortel, M.H.V. (1992). Structural basis of antigenic specificity and design of new vaccines. FASEB J, 6(14), 3265–3274.PubMedGoogle Scholar
  3. Arquint, O., Helbling, A., Crameri, R., et al. (1999). Reduced in vivo allergenicity of Bet v 1d isoform, a natural component of birch pollen. J Allergy Clin Immunol, 104(6), 1239–1243.PubMedCrossRefGoogle Scholar
  4. Beatrice, J.S., Astrid, R., Dirk, L.T., et al. (2005). Bet v 1142–156 is the dominant T-cell epitope of the major birch pollen allergen and important for cross-reactivity with Bet v1, Äìrelated food allergens. J Allergy Clin Immunol, 116(1), 213–219.CrossRefGoogle Scholar
  5. Bhalla, P.L., Singh, M.B. (2008). Biotechnology-based allergy diagnosis and vaccination. Trends Biotechnol, 26(3), 153–161.PubMedCrossRefGoogle Scholar
  6. Bohle, B., Radakovics, A., Luttkoft., D., et al. (2005). Characterization of the T cell response to the major hazelnut allergen, Cor a 1.04: Evidence for a relevant T-cell epitope not cross-reactive with homologous pollen allergens. Clin Exp Allergy, 35(10), 1392–1399.PubMedCrossRefGoogle Scholar
  7. Borges, J.P., Culerrier, R., Aldon, D., et al. (2010). GATEWAY (TM) technology and E. coli recombinant system produce a properly folded and functional recombinant allergen of the lipid transfer protein of apple (Mal d 3). Protein Expression and Purification, 70(2), 277–282.PubMedCrossRefGoogle Scholar
  8. Breiteneder, H., Ferreira, F., Hoffmannsommergruber, K., et al. (1993). Four recombinant isforms of Coralpha-1, the major allergen of Hazel pollen, show different IgE-binding properties. Eur J Biochem, 212(2), 355–362.PubMedCrossRefGoogle Scholar
  9. Bublin, M., Pfister, M., Radauer, C., et al. (2010). Component-resolved diagnosis of kiwifruit allergy with purified natural and recombinant kiwifruit allergens. J Allergy Clin Immunol, 125(3), 687–694.PubMedCrossRefGoogle Scholar
  10. Carnes, J., Himly, M., Gallego, M., et al. (2009). Detection of allergen composition and in vivo immunogenicity of depigmented allergoids of Betula alba. Clin Exp Allergy, 39(3), 426–434.PubMedCrossRefGoogle Scholar
  11. Crameri, R. (2001). High throughput screening: A rapid way to recombinant allergens. Allergy, 56, 30–34.PubMedCrossRefGoogle Scholar
  12. Crameri, R., Fluckiger, S., Glaser, A.G., et al. (2005). Recombinant allergens in research and clinics. Allergologie, 28(6), 215–218.Google Scholar
  13. Crameri, R., Jaussi, R., Menz, G., et al. (1994). Display of expression products of cDNA libraries on phage surfaces-A versatile screening system for selective isolation of genes by specific gene-product ligand interaction. Eur J Biochem, 226(1), 53–58.PubMedCrossRefGoogle Scholar
  14. de Marco, A. (2009). Strategies for successful recombinant expression of disulfide bond-dependent proteins in Escherichia coli. Microbial Cell Factories, 8, 26.PubMedCrossRefGoogle Scholar
  15. Diaz-Perales, A., Garcia-Casado, G., Sanchez-Monge, R., et al. (2002). cDNA cloning and heterologous expression of the major allergens from peach and apple belonging to the lipid-transfer protein family. Clin Exp Allergy, 32(1), 87–92.PubMedCrossRefGoogle Scholar
  16. Durham, S.R. (2006). Allergen immunotherapy (desensitisation) for allergic diseases. Clin Med, 6(4), 348–351.PubMedCrossRefGoogle Scholar
  17. Elmorjani, K., Lurquin, V., Lelion, A., et al. (2004). A bacterial expression system revisited for the recombinant production of cystine-rich plant lipid transfer proteins. Biochem Biophys Res Commun, 316(4), 1202–1209.PubMedCrossRefGoogle Scholar
  18. Fang, K.S.Y., Vitale, M., Fehlner, P., et al. (1988). cDNA cloning and primary structure of a white-face hornet venom allergen, antigen-5. PNAS, 85(3), 895–899.PubMedCrossRefGoogle Scholar
  19. Ferreira, F., Ebner, C., Kramer, B., et al. (1998). Modulation of IgE reactivity of allergens by site-directed mutagenesis: potential use of hypoallergenic variants for immunotherapy. FASEB J, 12(2), 231–242.PubMedGoogle Scholar
  20. Fuchs, H.C., Bohle, B., Dall’Antonia, Y., et al. (2006). Natural and recombinant molecules of the cherry allergen Pru av 2 show diverse structural and B-cell characteristics but similar T-cell reactivity. Clin Exp Allergy, 36(3), 359–368.PubMedCrossRefGoogle Scholar
  21. Gadermaier, G., Harrer, A., Girbl, T., et al. (2009). Isoform identification and characterization of Art v 3, the lipid-transfer protein of mugwort pollen. Molr Immunol, 46(10), 1919–1924.CrossRefGoogle Scholar
  22. Gajhede, M., Osmark, P., Poulsen, F.M., et al. (1996). X-ray and NMR structure of Bet v 1, the origin of birch pollen allergy. Nat Structural Biol, 3(12), 1040–1045.CrossRefGoogle Scholar
  23. Gamboa, P.M., Sanz, M.L., Lombardero, M., et al. (2009). Component-resolved in vitro diagnosis in peach-allergic patients. J Investig Allergol Clin Immunol, 19(1), 13–20.PubMedGoogle Scholar
  24. Gincel, E., Simorre, J.P., Cailleet, A., et al. (1994). Three-dimensional structure in solution of a wheat lipid-transfer protein from multidimensional H-1-NMR data-a new folding for lipid carriers. Eur J Biochem, 226(2), 413–422.PubMedCrossRefGoogle Scholar
  25. Glenting. J., Poulsen, L.K., Kato, K., et al. (2007). Production of recombinant peanut allergen Ara h 2 using Lactococcus lactis. Microbial Cell Factories, 6, 28.PubMedCrossRefGoogle Scholar
  26. Hiller, R., Laffer, S., Harwanegg, C., et al. (2002). Microarrayed allergen molecules: diagnostic gatekeepers for allergy treatment. FASEB J, 16(1), 414–416.PubMedGoogle Scholar
  27. Hoffmann-Sommergruber, K., Ferris, R., Pec, M., et al. (2000). Characterization of Api g 1.0201, a new member of the Api g 1 family of celery allergens. Int Arch Allergy Immunol, 122(2), 115–123PubMedCrossRefGoogle Scholar
  28. Holm, J., Gajhede, M., Ferreras, M., et al. (2004). Allergy vaccine engineering: Epitope modulation of recombinant Bet v 1 reduces IgE binding but retains protein folding pattern for induction of protective blocking-antibody responses. J Immunol, 173(8), 5258–5267.PubMedGoogle Scholar
  29. Jutel, M., Jaeger, L., Suck, R., et al. (2005). Allergen-specific immunotherapy with recombinant grass pollen allergens. J Allergy Clin Immunol, 116(3), 608–613.PubMedCrossRefGoogle Scholar
  30. Kettner, J., Meyer, H., Cromwell, O., et al. (2007). Specific immunotherapy with recombinant birch pollen allergen rBet v 1-FV results of 2 years of treatment (Phase II trial). Allergy, 62(s83), 262–262.Google Scholar
  31. Le, L. Q., Lorenz, Y., Scheurer, S., et al. (2006). Design of tomato fruits with reduced allergenicity by dsRNAi-mediated inhibition of ns-LTP (Lyc e 3) expression. Plant Biotech J, 4(2), 231–242.CrossRefGoogle Scholar
  32. Liao, E.C., Hsu, E.L., Tsai, J.J., et al. (2009). Immunologic characterization and Allergenicity of Recombinant Tyr p 3 allergen from the storage mite tyrophagus putrescentiae. Int Arch Allergy Immunol, 150(1), 15–24.PubMedCrossRefGoogle Scholar
  33. Lienard, D., Dinh, O.T., van Oort, E., et al. (2007). Suspension-cultured BY-2 tobacco cells produce and mature immunologically active house dust mite allergens. Plant Biotechnol J, 5(1), 93–108.PubMedCrossRefGoogle Scholar
  34. Lorenz, A.R., Scheurer, S., Haustein, D., et al. (2001). Recombinant food allergens. J Chromatogr B-Analytical Technologies in the Biomedical and Life Sciences, 756(1–2), 255-279.Google Scholar
  35. Luttkopf, D., Muller, U., Skov, P.S., et al. (2002). Comparison of four variants of a major allergen in hazelnut (Corylus avellana) Cor a 1.04 with the major hazel pollen allergen Cor a 1.01. Mol Immunol, 38(7), 515–525.PubMedCrossRefGoogle Scholar
  36. Ma, Y., Gadermaier, G., Bohle, B., et al. (2006). Mutational analysis of amino acid positions crucial for IgE-binding epitopes of the major apple (Malus domestica) allergen, Mal d 1. Int Arch Allergy Immunol, 139(1), 53–62.PubMedCrossRefGoogle Scholar
  37. Ma, Y., Zuidmeer, L., Bohle, B., et al. (2006). Characterization of recombinant Mal d 4 and its application for component-resolved diagnosis of apple allergy. Clin Exp Allergy, 36(8), 1087–1096.PubMedCrossRefGoogle Scholar
  38. Metz-Favre, C., Linhart, B., Focke-Tejkl, M., et al. (2007). Skin test diagnosis of grass pollen allergy with a recombinant hybrid molecule. J Allergy Clin Immunol, 120(2), 315–321.PubMedCrossRefGoogle Scholar
  39. Mirza, O., Henriksen, A., Ipsen, H., et al. (2000). Dominant epitopes and allergic cross-reactivity: Complex formation between a Fab fragment of a monoclonal murine IgG antibody and the major allergen from birch pollen Bet v 1. J Immunol, 165(1), 331–338.PubMedGoogle Scholar
  40. Moser, M., Crameri, R., Brust, E., et al. (1994). Diagnostic value of recombinant aspergillus-fumigatus allergen I/A for skin testing and serology. J Allergy Clin Immunol, 93(1), 1–11.PubMedCrossRefGoogle Scholar
  41. Mutschlechner, S., Deifl, S., Bohle, B. (2009). Genetic allergen modification in the development of novel approaches to specific immunotherapy. Clin Exp Allergy, 39(11), 1635–1642.PubMedCrossRefGoogle Scholar
  42. Nelson, H.S. (2007). Allergen immunotherapy: where is it now? J Allergy Clinl Immunol, 119(4), 769–777.CrossRefGoogle Scholar
  43. Neudecker, P., Lehmann, K., Nerkamp, J., et al. (2003). Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): Correlating IgE reactivity with three-dimensional structure. Biochem J, 376, 97–107.PubMedCrossRefGoogle Scholar
  44. Niederberger, V., Horak, F., Vrtala, S., et al. (2004). Vaccination with genetically engineered allergens prevents progression of allergic disease. PNAS, 101, 14677–14682.PubMedCrossRefGoogle Scholar
  45. Olsson, S., Van Hage-Hamsten, M., Whitley, P., et al. (1998). Expression of two isoforms of Lep d 2, the major allergen of Lepidoglyphus destructor, in both prokaryotic and eukaryotic systems. Clin Exp Allergy, 28(8), 984–991.PubMedCrossRefGoogle Scholar
  46. Palacin, A., Varela, J., Quirce, S., et al. (2009). Recombinant lipid transfer protein Tri a 14: a novel heat and proteolytic resistant tool for the diagnosis of baker’s asthma. Clin Exp Allergy, 39(8), 1267–1276.PubMedCrossRefGoogle Scholar
  47. Pasquato, N., Berni, R., Folli, C., et al. (2006). Crystal structure of peach Pru p 3, the prototypic member of the family of plant non-specific lipid transfer protein pan-allergens. J Mol Biol, 356(3), 684–694.PubMedCrossRefGoogle Scholar
  48. Pauli, G., Larsen, T.H., Rak, S., et al. (2008). Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic rhinoconjunctivitis. J Allergy Clin Immunol, 122(5), 951–960.PubMedCrossRefGoogle Scholar
  49. Pittner, G., Vrtala, S., Thomas, W.R., et al. (2004). Component-resolved diagnosis of house-dust mite allergy with purified natural and recombinant mite allergens. Clin Exp Allergy, 34(4), 597–603.PubMedCrossRefGoogle Scholar
  50. Pokoj, S., Lauer, I., Fotisch, K., et al. (2010). Pichia pastoris is superior to E-coli for the production of recombinant allergenic non-specific lipid-transfer proteins. Protein Expression and Purification, 69(1), 68–75.PubMedCrossRefGoogle Scholar
  51. Poltl, G., Ahrazem O., Paschinger, K., et al. (2007). Molecular and immunological characterization of the glycosylated orange allergen Cit s 1. Glycobiology, 17(2), 220–230.PubMedCrossRefGoogle Scholar
  52. Pons, L., Burks, W. (2005). Novel treatments for food allergy. Expert Opin Investig Drugs, 14(7), 829–834.PubMedCrossRefGoogle Scholar
  53. Reuter, A., Fortunato, D., Garoffo, L.P., et al. (2005). Novel isoforms of Pru av 1 with diverging immunoglobulin E binding properties identified by a synergistic combination of molecular biology and proteomics. Proteomics, 5(1), 282–289.PubMedCrossRefGoogle Scholar
  54. Rhyner, C., Weichel, M., Fluckiger, S., et al. (2004). Cloning allergens via phage display. Methods, 32(3), 212–218.PubMedCrossRefGoogle Scholar
  55. Rolland, J.M., Gardner, L.M., O’Hehir, R.E., et al. (2009). Allergen-related approaches to immunotherapy. Pharmacology and Therapeutics, 121(3), 273–284.PubMedCrossRefGoogle Scholar
  56. Scheurer, S., Pastorello, E.A., Wangorsch, A., et al. (2001). Recombinant allergens Pro av 1 and Pru av 4 and a newly identified lipid transfer protein in the in vitro diagnosis of cherry allergy. J Allergy Clin Immunol, 107(4), 724–731.CrossRefGoogle Scholar
  57. Schmidt, M., McConnell, T.J., Hoffman, D.R. (2003). Immunologic characterization of the recombinant fire ant venom allergen Sol i 3. Allergy, 58(4), 342–349.PubMedCrossRefGoogle Scholar
  58. Schramm, G., Kahlert, H., Suck, R., et al. (1999). “Allergen engineering”: Variants of the timothy grass pollen allergen Phl p 5b with reduced IgE-binding capacity but conserved T-Cell reactivity. J Immunol, 162(4), 2406–2414.PubMedGoogle Scholar
  59. Sirvent, S., Palomares, O., Vereda, A., et al. (2009). nsLTP and profilin are allergens in mustard seeds: cloning, sequencing and recombinant production of Sin a 3 and Sin a 4. Clinical and Experimental Allergy, 39(12), 1929–1936.PubMedCrossRefGoogle Scholar
  60. Tanyaratsrisakul, S., Malainual, N., Jirapongsananuruk, O., et al. (2010). Structural and IgE Binding Analyses of Recombinant Der p 2 Expressed from the Hosts Escherichia coli and Pichia pastoris. Int Arch Allergy Immunol, 151(3), 190–198.PubMedCrossRefGoogle Scholar
  61. Tordesillas, L., Cuesta-Herranz, J., Gonzalez-Munoz, M., et al. (2008). T-cell epitopes of the major peach allergen, Pru p 3: Identification and differential T-cell response of peach-allergic and non-allergic subjects. Mol Immunol, 46(4), 722–728.PubMedCrossRefGoogle Scholar
  62. Valenta, R., Duchene, M., Vrtala, S., et al. (1991). Recombinant allergens for immunoblot diagnosis of tree pollen allergy. J Allergy Clin Immunol, 88(6), 889–894.PubMedCrossRefGoogle Scholar
  63. Valenta, R., Kraft, D. (1995). Recombinant allergens for diagnosis and therapy of allergic diseases. Current Opinion in Immunology, 7(6), 751–756.PubMedCrossRefGoogle Scholar
  64. Valenta, R., Lidholm, J., Niederberger, V., et al. (1999). “The recombinant allergen-based concept of component-resolved diagnostics and immunotherapy (CRD and CRIT)”. Clin Exp Allergy, 29(7), 896–904.PubMedCrossRefGoogle Scholar
  65. Valenta, R., Ferreira, F., Focke-Tejkl, M., et al. (2010). “From Allergen Genes to Allergy Vaccines”. Annual Review of Immunol, 28(28), 211–241.CrossRefGoogle Scholar
  66. Valenta, R., Niederberger, V. (2007). Recombinant allergens for immunotherapy. J Allergy Clin Immunol, 119(4), 826–830.PubMedCrossRefGoogle Scholar
  67. van Overtvelt, L., Batard, T., Fadel, R., et al. (2006). Immune mechanisms of allergen-specific sublingual immunotherapy. Revue Francaise D Allergologie Et D Immunologie Clinique, 46(8), 713–720.CrossRefGoogle Scholar
  68. van Ree R. (2004). The CREATE project: EU support for the improvement of allergen standardization in Europe. Allergy, 59(6), 571–574.PubMedCrossRefGoogle Scholar
  69. van Ree, R., Chapman, M.D., Ferreira, F., et al. (2008). The CREATE Project: development of certified reference materials for allergenic products and validation of methods for their quantification. Allergy, 63(3), 310–326.PubMedCrossRefGoogle Scholar
  70. Vanekkrebitz, M., Hoffmannsommergruber, K., Machado, M.L.D., et al. (1995). Cloning and sequencing of Mal d 1, the major allergen from apple (Malus-domestica), and its immunological relationship to Bet v 1, the major birch pollen allergen, Biochemical and Biophysical Research Communications, 214(2), 538–551.CrossRefGoogle Scholar
  71. Verdino, P., Barderas, R., Villalba, M., et al. (2008). Three-dimensional structure of the cross-reactive pollen allergen Che a 3: Visualizing cross-reactivity on the molecular surfaces of weed, grass, and tree pollen allergens. J Immunol, 180(4), 2313–2321.PubMedGoogle Scholar
  72. Wallner, M., Gruber, P., Radauer, C., et al. (2004). Lab scale and medium scale production of recombinant allergens in Escherichia coli. Methods, 32(3), 219–226PubMedCrossRefGoogle Scholar
  73. Willerroider, M., Fuchs, H., Ballmer-Webe, B.K., et al. (2003). Cloning and molecular and immunological characterisation of two new food allergens, Cap a 2 and Lyc e 1, profilins from bell pepper (Capsicum annuum) and tomato (Lycopersicon esculentum). Int Arch Allergy Immunol, 131(4), 245–255PubMedCrossRefGoogle Scholar
  74. Wohrl, S., Vigl, K., Zehetmayer, S., et al. (2006). The performance of a component-based allergen-microarray in clinical practice. Allergy, 61(5), 633–639.PubMedCrossRefGoogle Scholar
  75. Yssel, H., Johnson, K. E., Schneider, P.V., et al. (1992). T-cell activation inducing epitopes of the house dust mite allergen Der p 1. Proliferation and lymphokine production patterns by Der p 1-specific CD4+ T-cell clones. J Immunol, 148(3), 738–745.Google Scholar
  76. Zuidmeer, L., van Leeuwen, W.A., Budde, I.K., et al. (2005). Lipid transfer proteins from fruit: Cloning, expression and quantification. Int Arch Allergy Immunol, 137(4), 273–281.PubMedCrossRefGoogle Scholar

Copyright information

© Zhejiang University Press, Hangzhou and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Ying-Tao Ma
    • 1
  • Zhao-Wei Yang
    • 1
  • Zhong-Shan Gao
    • 1
  1. 1.Allergy Research Center/Department of HorticultureZhejiang UniversityHangzhouChina

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