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Engineering of the major house dust mite allergen Der f 2 for allergen-specific immunotherapy

Abstract

A major problem with allergen-specific immunotherapy involving repeated injections of allergens is the risk of an anaphylactic reaction. We engineered the major house dust mite allergen, Der f 2, to reduce its capacity to induce skin test reactivity and histamine release from peripheral blood basophils in allergic patients. The engineered allergen, in which the disulfide bond that linked the N- and C-terminal sequences of Der f 2 was disrupted, retained T-cell epitopes essential for immunotherapy and ability to stimulate T-cell proliferation. Such engineered allergens are potentially useful for safer and more effective immunotherapy for allergies.

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References

  1. Moffatt, M.F., Hill, M.R., Cornélls, F., Schou, C., Faux, J.A., Young, R.P., et al. 1994. Genetic linkage of T-cell receptor alfa/delta complex to specific IgE responses. Lancet 343: 1597–1600.

    Article  CAS  Google Scholar 

  2. Marsh, D.G., Neely, J.D., Breazeale, D.R., Ghosh, B., Freidhoff, L.R., Ehrlich-Kautzky, E., et al. 1994. Linkage analysis of IL4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations. Science 264: 1152–1156.

    Article  CAS  Google Scholar 

  3. Noon, L. 1911. Prophylactic inoculation against hay fever. Lancet i: 1572–1573.

    Article  Google Scholar 

  4. Hoyne, G.F., Kristensen, N.M., Yssel, H., and Lamb, J.R. 1995. Peptide modulation of allergen-specific immune responce. Curr. Opin. Immunol. 7: 757–761.

    Article  CAS  Google Scholar 

  5. Norman, P.S., Ohman, J.L. Jr., Long, A.A., Creticos, P.S., Gefter, M.A., Shaked, Z., et al. 1996. Treatment of cat allergy with T-cell reactive peptides. Am. J. Respir. Crit. Care. Med. 154: 1623–1628.

    Article  CAS  Google Scholar 

  6. van Neerven, R.J.J., Ebner, C., Yssel, H., Kapsenberg, M.L., and Lamb, J.R. 1996. T-cell responses to allergens: epitope-specificity and clinical relevance. Immunol. Today 17: 526–532.

    CAS  Google Scholar 

  7. van't Hof, W., Dridijk, P.C., van den Berg, M., Beck-Sickinger, A.G., Jung, G., and Aalberse, R.C. 1991. Epitope mapping of the Dermatophagoides pteronyssinus house dust mite major allergen Der p II using overlapping synthetic peptides. Mol. Immunol. 28: 1225–1232.

    Article  CAS  Google Scholar 

  8. Ishizaka, T. and Ishizaka, K. 1984. Activation of mast cells for mediator release through IgE. Prog. Allergy 34: 188–235.

    CAS  Google Scholar 

  9. Metzger, H., Alcaraz, G., Hohman, R., Kinet, J.-P., Pribluda, V., and Quarto, R. 1986. The receptor with high affinity for immunoglobulin. E. Annu. Rev. Immunol. 4: 419–470.

    Article  CAS  Google Scholar 

  10. WHO nomenclature committee for factors of the HLA system. 1995. Nomenclature for factors of the HLA system 1995. Vox Sang. 69: 359–372.

  11. Davis, M.M. 1990. T cell receptor gene diversity and selection. Annu. Rev. Biochem. 59: 475–496.

    Article  CAS  Google Scholar 

  12. O'Brien, R.M., Thomas, W.R., Nicholson, I., Lamb, J.R., and Tait, B.D. 1995. An immunogenic analysis of the T-cell recognition of the major house dust mite allergen Der p 2: Identification of high and low-responder HLA-DQ alleles and localization of T-cell epitopes. Immunology 86: 176–182.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Yssel, H., Johonson, K.E., Schneider, P.V., Wideman, J., Terr, A., Kastelein, R., and de Vries, J.E. 1992. T cell activation-inducing epitopes of the house dust mite allergen Der p I. Proliferation and lymphokine production patterns by Der p l-Specific CD4+T cell clones. J. Immunol. 148: 738–745.

    CAS  PubMed  Google Scholar 

  14. Platts-Mills, T.A.E. and Weck, A.L. 1989. Dust mite allergens and asthma—A worldwide problem. J. Allergy Clin. Immunol. 83: 416–427.

    Article  Google Scholar 

  15. Voohorst, R., Spieksma-Boezeman, M.I.A., Spieksma, F.T.M., Varekamp, H., Leupen, M.J., and Lyklema, A.W. 1967. The house dust mite (Dermatophagoides pteronyssinus) and the allergens it produces. Identity with the house dust allergen. J. Allergy 39: 325–339.

    Article  Google Scholar 

  16. Miyamoto, T., Oshima, S., Ishizaki, T., and Sano, S. 1968. Allergic identity between the common floor mite (Dermatophagoides farinae Hughes 1961) and house dust as a causative agent in bronchial asthma. J. Allergy 42: 14–28.

    Article  CAS  Google Scholar 

  17. Platts-Mills, T.A.E. and Chapman, M.D. 1987. Dust mites: Immunology, allergic disease, and environmental control. J. Allergy Clin. Immunol. 80: 755–775.

    Article  CAS  Google Scholar 

  18. Haida, M., Okudaira, H., Ogita, T., Ito, K., Miyamoto, T., Nakajima, T., and Hongo, I. 1985. Allergens of the house dust mite Dermatophagoides farinae-Immunochemical studies of four allergic fractions. J. Allergy Clin. Immunol. 75: 686–692.

    Article  CAS  Google Scholar 

  19. Yamashita, N., Haida, M., Suko, M., Okudaira, H., and Miyamoto, T. 1989. Allergens of house dust mite Dermatophagoides farinae. II. Immunological characterization of four allergic molecules. Int. Arch. Allergy Appl. Immunol. 88: 173–175.

    Article  CAS  Google Scholar 

  20. Lombardero, M., Heymann, P.W., Platts-Mills, T.A.E., Fox, J.W., and Chapman, M.D. 1990. Conformational stability of B cell epitopes on group I and group II Dermatophagoides spp. allergens. Effect of thermal and chemical denaturation on the binding of mouse IgG and human IgE antibodies. J. Immunol. 144: 1353–1360.

    CAS  PubMed  Google Scholar 

  21. Nishiyama, C., Fukada, M., Usui, Y., Iwamoto, N., Yuuki, T., Okumura, Y., and Okudaira, H. 1995. Analysis of the IgE-epitope of Der f 2, a major mite allergen, by in vitro mutagenesis. Mol. Immunol. 32: 1021–1029.

    Article  CAS  Google Scholar 

  22. Smith, A.M. and Chapman, M.D. 1996. Reduction in IgE binding to allergen variants generated by site-directed mutagenesis: contribution of disulfide bonds to the antigenic structure of the major house dust mite allergen Der p 2. Mol. Immunol. 33: 399–405.

    Article  CAS  Google Scholar 

  23. Takai, T., Yuuki, T., Okumura, Y., Mori, A., and Okudaira, H. 1997. Determination of the N- and C-terminal sequences required to bind human IgE of the major house dust mite allergen Der f 2 and epitope mapping for monoclonal antibodies. Mol. Immunol. In press.

  24. van Neerven, R.J.J., van't Hof, W., Ringrose, J.H., Jansen, H.M., Aalberse, R.C., Wierenga, E.A., and Kapsenberg, M.L. 1993. T cell epitopes of house dust mite allergen Der p II. J. Immunol. 151: 2326–2335.

    CAS  Google Scholar 

  25. O'Hehier, R.E., Verhoef, A., Panagiotopoulou, E., Keswani, S., Hayball, J.D., Thomas, W.R., and Lamb, J.R. 1993. Analysis of human T cell responses to the group II allergen of Dermatophagoides species: localization of major antigenic sites. J. Allergy Clin. Immunol. 92: 105–113.

    Article  Google Scholar 

  26. Tsitoura, D.C., Verhoef, A., Gelder, C.M., O'Hehir, R.E., and Lamb, J.R. 1996. Altered T cell ligands derived from a major house dust mite allergen enhance IFN-γ but not IL-4 production by human CD4+ T cells. J. Immunol. 157: 2160–2165.

    CAS  PubMed  Google Scholar 

  27. Valenta, R. and Kraft, D. 1995. Recombinant allergens for diagnosis and therapy of allergic diseases. Curr. Opin. Immunol. 7: 751–756.

    Article  CAS  Google Scholar 

  28. Yuuki, T., Okumura, Y., Ando, T., Yamakawa, H., Suko, M., Haida, M., and Okudaira, H. 1990. Cloning and sequencing of cDNAs corresponding to mite major allergen Der f II. Jpn. J. Allergol. 39: 557–561.

    CAS  Google Scholar 

  29. Yuuki, T., Okumura, Y., Ando, T., Yamakawa, H., Suko, M., Haida, M., and Okudaira, H. 1991. Cloning and expression of cDNA coding for the major house dust mite allergen Der f II in Escherichia coli. Agric. Biol. Chem. 55: 1233–1238.

    CAS  PubMed  Google Scholar 

  30. Nishiyama, C., Yuuki, T., Takai, T., Okumura, Y., and Okudaira, H. 1993. Determination of three disulfide bonds in a major house dust mite allergen, Der f II. Int. Arch. Allergy Immunol. 101: 159–166.

    Article  CAS  Google Scholar 

  31. Secrist, H., DeKruyff, R.H., and Umets, D.T. 1995. Interleukin 4 production by CD4+ T cells from allergic individuals is modulated by antigen concentration and antigen-presenting cell type. J. Exp. Med. 181: 1081–1089.

    Article  CAS  Google Scholar 

  32. Suko, M., Mori, A., Ito, K., and Okudaira, H. 1995. Oral immunotherapy may induce T cell anergy. Int. Arch. Allergy Immunol. 107: 278–281.

    Article  CAS  Google Scholar 

  33. O'Brien, R.M., Byron, K.A., Varigos, G.A., and Thomas, W.R. 1997. House dust mite immunotherapy results in decrease in Der p 2-specific IFN-γ and IL-4 expression by circulating T lymphocytes. Clin. Exp. Allergy 27: 46–51.

    Article  CAS  Google Scholar 

  34. Akagawa, M., Mori, T., Ando, T., and Okudaira, H. 1992. Specific measurement of a major mite allergen, by an enzyme-linked immunosorbent assay system using monoclonal anti-Der f II antibodies. Biosci. Biotech. Biochem. 56: 1725–1727.

    Article  CAS  Google Scholar 

  35. Dredog, S. 1985. Skin prick test. Allergy 40: 55–59.

    Google Scholar 

  36. Norman, P.S. 1993. Modern concepts of immunotherapy. Curr. Opin. Immunol. 5: 968–973.

    Article  CAS  Google Scholar 

  37. Parronchi, P., Macchia, D., Piccinni, M.-P., Biswas, P., Simonelli, C., Maggi, E., et al. 1991. Allergen- and bacterial antigen-specific T-cell clones established from atopic donors show a different profile of cytokine production. Proc. Natl. Acad. Sci. USA 88: 4538–4542.

    Article  CAS  Google Scholar 

  38. Nishiyama, C., Yuuki, T., Usui, Y., Iwamoto, N., Okumura, Y., and Okudaira, H. 1994. Effects of amino acid variations in recombinant Der f II on its human IgE and mouse IgG recognition. Int. Arch. Allergy Immunol. 105: 62–69.

    Article  CAS  Google Scholar 

  39. Pruzansky, J.J., Grammer, L.C., Patterson, R., and Roberts, M. 1983. Dissociation of IgE from receptors on human basophils: I. Enhanced passive immunization for histamine release. J. Immunol. 131: 1949–1953.

    CAS  PubMed  Google Scholar 

  40. Mori, A., Suko, M., Kaminuma, O., Inoue, S., Ohmura, Y., Nishizaki, Y., et al. 1996. IL-15 promotes cytokine production of human helper T cells. J. Immunol. 156: 2400–2405.

    CAS  PubMed  Google Scholar 

  41. Mori, A., Kaminuma, O., Suko, M., Inoue, S., Ohmura, T., Hoshino, A., et al. 1997. Two distinct pathways of interleukin-5 synthesis in allergen-specific human T-cell clones are suppressed by glucocorticoids. Blood. In press.

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Correspondence to Toshiro Takai.

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Takai, T., Yokota, T., Yasue, M. et al. Engineering of the major house dust mite allergen Der f 2 for allergen-specific immunotherapy. Nat Biotechnol 15, 754–758 (1997). https://doi.org/10.1038/nbt0897-754

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