Nature Biotechnology
15, 754 - 758 (1997)
doi:10.1038/nbt0897-754
Engineering of the major house dust mite allergen Der f 2 for allergen-specific immunotherapyToshiro Takai1, *, Toyokazu Yokota1, Masaaki Yasue1, Chiharu Nishiyama1, Toshifumi Yuuki1, Akio Mori2, Hirokazu Okudaira2
& Yasushi Okumura1
1Biosience Research and Development Laboratory, Asahi Breweries, Ltd., 1-1-21 Midori, Moriya-cho, Kita-sohma-gun, Ibaraki 302-01, Japan.
2Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.
*e-mail: toshiro.takai@asahibeer.co.jp. 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. REFERENCES
- 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 | PubMed | ISI | ChemPort |
- 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. | PubMed | ISI | ChemPort |
- Noon, L. 1911. Prophylactic inoculation against hay fever. Lancet i: 1572−1573. | Article |
- 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 | PubMed | ISI | ChemPort |
- 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. | PubMed | ISI | ChemPort |
- 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. | Article | ChemPort |
- 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 | PubMed | ChemPort |
- Ishizaka, T. and Ishizaka, K. 1984. Activation of mast cells for mediator release through IgE. Prog. Allergy 34: 188−235. | PubMed | ISI | ChemPort |
- 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 | ChemPort |
- WHO nomenclature committee for factors of the HLA system. 1995. Nomenclature for factors of the HLA system 1995. Vox Sang. 69: 359−372. | ISI |
- Davis, M.M. 1990. T cell receptor gene diversity and selection. Annu. Rev. Biochem. 59: 475−496. | Article | PubMed | ISI | ChemPort |
- 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. | PubMed | ChemPort |
- 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. | PubMed | ISI | ChemPort |
- Platts-Mills, T.A.E. and Weck, A.L. 1989. Dust mite allergens and asthmaA worldwide problem. J. Allergy Clin. Immunol. 83: 416−427. | PubMed |
- 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.
- 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. | PubMed | ISI | ChemPort |
- 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. | PubMed | ChemPort |
- 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. | PubMed | ISI | ChemPort |
- 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. | PubMed | ISI | ChemPort |
- 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. | PubMed | ISI | ChemPort |
- 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 | PubMed | ISI | ChemPort |
- 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 | PubMed | ISI | ChemPort |
- 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. | PubMed |
- 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. | PubMed | ChemPort |
- 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. | PubMed |
- 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-
but not IL-4 production by human CD4+ T cells. J. Immunol. 157: 2160−2165. | PubMed | ISI | ChemPort |
- Valenta, R. and Kraft, D. 1995. Recombinant allergens for diagnosis and therapy of allergic diseases. Curr. Opin. Immunol. 7: 751−756. | Article | PubMed | ISI | ChemPort |
- 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. | ChemPort |
- 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. | PubMed | ISI | ChemPort |
- 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. | PubMed | ISI | ChemPort |
- 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. | PubMed | ISI | ChemPort |
- Suko, M., Mori, A., Ito, K., and Okudaira, H. 1995. Oral immunotherapy may induce T cell anergy. Int. Arch. Allergy Immunol. 107: 278−281. | PubMed | ISI | ChemPort |
- 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-
and IL-4 expression by circulating T lymphocytes. Clin. Exp. Allergy 27: 46−51. | Article | PubMed | ChemPort |
- 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. | ISI | ChemPort |
- Dredog, S. 1985. Skin prick test. Allergy 40: 55−59.
- Norman, P.S. 1993. Modern concepts of immunotherapy. Curr. Opin. Immunol. 5: 968−973. | Article | PubMed | ISI | ChemPort |
- 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. | PubMed | ChemPort |
- 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. | PubMed | ISI | ChemPort |
- 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. | PubMed | ISI | ChemPort |
- 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. | PubMed | ISI | ChemPort |
- 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. | PubMed |
|