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  • 1
    Hopkin, J. M., Mechanisms of enhanced prevalence of asthma and atopy in developed countries. Curr. Opin. Immunol. 1997. 9: 788792.
  • 2
    Akdis, C. A., Blesken, T., Wymann, D., Akdis, M. and Blaser, K., Differential regulation of human T cell cytokine patterns and IgE and IgG4 responses by conformational antigen variants. Eur. J. Immunol. 1998. 28: 914925.
  • 3
    Akdis, C. A., Akdis, M., Blesken, T., Wymann, D., Alkan, S. S., Müller, U. and Blaser, K., Epitope specific T cell tolerance to phospholipase A2 in bee venom immunotherapy and recovery by IL-2 and IL-15 in vitro. J. Clin. Invest. 1996. 98: 16761683.
  • 4
    Müller, U. R., Dudler, T., Schneider, T., Crameri, R., Fischer, H., Skrbic, D., Maibach, , et al., Type 1 skin reactivity to native and recombinant phospholipase A2 from honey bee venom is similar. J. Allergy Clin. Immunol. 1995. 96: 395402.
  • 5
    Soldatova, L. N., Crameri, R., Gmachl, M., Kemeny, D. M., Schmidt, M., Weber, M. and Mueller, U. R., Superior biologic activity of the recombinant bee venom allergen hyaluronidase expressed in baculovirus-infected insect cells as compared with Escherichia coli. J. Allergy Clin. Immunol. 1998. 101: 691698.
  • 6
    Paull, B. R., Yunginger, J. W. and Gleich, G. J., Melittin: an allergen of honeybee venom. J. Allergy Clin. Immunol. 1977. 59: 334338.
  • 7
    Nish, W. A., Charlesworth, E. N., Davis, T. L., Whisman, B. A., Valtier, S., Charlesworth, M. G. and Lieferman, K. M., The effect of immunotherapy on the cutaneous late phase response to antigen. J. Allergy Clin. Immunol. 1994. 93: 484493.
  • 8
    Bentley, A. M., Jacobson, M. R., Cumberworth, V., Barkans, J. R., Moqbel, R. and Schwartz, L. B., Immunohistology of the nasal mucosa in seasonal allergic rhinitis: increases in activated eosinophils and epithelial mast cells. J. Allergy Clin. Immunol. 1992. 89: 877883.
  • 9
    Akdis, C. A. and Blaser, K., Bypassing IgE and targeting T cells for specific immunotherapy of allergy. Trends Immunol. 2001. 22: 175178.
  • 10
    Van der Heijden, F. L., van Neerven, R. J. J., van Katwijk, M., Bos, J. D. and Kapsenberg, M. L., Serum IgE-facilitated allergen presentation in allergic disease. J. Immunol. 1993. 150: 36433647.
  • 11
    Waldmann, T. A., Immunotherapy: Past, present and future. Nat. Med. 2003. 9: 269277.
  • 12
    Dudler, T., Schneider, T., Annand, R. R., Gelb, M. H. and Suter, M., Antigenic surface of the bee venom allergen phospholipase A2. Structural and functional analysis of human IgG4 antibodies reveals potential role in protection. J. Immunol. 1994. 152: 55145522.
  • 13
    Moverare, R., Elfman, L., Vesterinen, E., Metso, T. and Haahtela, T., Development of new IgE specificities to allergenic components in birch pollen extract during specific immunotherapy studied with immunoblotting and Pharmacia CAP System. Allergy 2002. 57: 423430.
  • 14
    Scott, D. L., Otwinowski, Z., Gelb, M. H. and Sigler, P. B., Crystal structure of bee-venom phospholipase A2 in a complex with a transition-state analogue. Science 1990. 250: 15631566.
  • 15
    Owen, M. D. and Pfaff, L. A., Melittin synthesis in the venom system of the honey bee (Apis mellifera L.). Toxicon 1995. 33: 11811188.
  • 16
    Werkmeister, J. A., Kirkpatrick, A., McKenzie, J. A. and Rivett, D. E., The effect of sequence variations and structure on the cytolytic activity of melittin peptides. Biochim. Biophys. Acta 1993. 1157: 5054.
  • 17
    Carballido, J. M., Carballido-Perrig, N., Kägi, M. K., Meloen, R. H., Wüthrich, B., Heusser, C. H. and Blaser, K., T cell epitope specificity in human allergic and non-allergic subjects to bee venom phospholipase A2. J. Immunol. 1993. 150: 35823591.
  • 18
    Faith, A., Akdis, C. A., Akdis, M., Simon, H.-U. and Blaser, K., Defective TCR stimulation in anergized type 2 T helper cells correlates with abrogated p56lck and ZAP-70 tyrosine kinase activities. J. Immunol. 1997. 159: 5360.
  • 19
    Akdis, C. A., Blesken, T., Akdis, M., Wüthrich, B. and Blaser, K., Role of IL-10 in specific immunotherapy. J. Clin. Invest. 1998. 102: 98106.
  • 20
    Larche, M. and Wraith, D. C., Peptide-based therapeutic vaccines for allergic and autoimmune diseases. Nat. Med. 2005. 11: S69–S76.
  • 21
    Akdis, M., Verhagen, J., Taylor, A., Karamloo, F., Karagiannidis, C., Crameri, R., Thunberg, S., et al., Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J. Exp. Med. 2004. 199: 15671575.
  • 22
    Müller, U. R., Akdis, C. A., Fricker, M., Akdis, M., Bettens, F., Blesken, T. and Blaser, K., Successful immunotherapy with T cell epitope peptides of bee venom phospholipase A2 induces specific T cell anergy in bee sting allergic patients. J. Allergy Clin. Immunol. 1998. 101: 747754.
  • 23
    Woodfolk, J. A., Sung, S. S., Benjamin, D. C., Lee, J. K. and Platts-Mills, T. A., Distinct human T cell repertoires mediate immediate and delayed-type hypersensitivity to the Trichophyton antigen, Tri r 2. J. Immunol. 2000. 165: 43794387.
  • 24
    Vrtala, S., Akdis, C. A., Budak, F., Akdis, M., Blaser, K., Kraft, D. and Valenta, R., T cell epitope-containing hypoallergenic recombinant fragments of the major birch pollen allergen, Bet v 1, induce blocking antibodies. J. Immunol. 2000. 165: 66536659.
  • 25
    Linhart, B., Jahn-Schmid, B., Verdino, P., Keller, W., Ebner, C., Kraft, D. and Valenta, R., Combination vaccines for the treatment of grass pollen allergy consisting of genetically engineered hybrid molecules with increased immunogenicity. FASEB J. 2002. 16: 13011303.
  • 26
    Niederberger, V., Horak, F., Vrtala, S., Spitzauer, S., Krauth, M. T., Valent, P., Reisinger, J., et al., Vaccination with genetically engineered allergens prevents progression of allergic disease. Proc. Natl. Acad. Sci. USA 2004. 101 Suppl. 2: 1467714682.
  • 27
    Laver, W. G., Air, G. M., Webster, R. G. and Smith-Gill, S. J., Epitopes on protein antigens: misconceptions and realities. Cell 1990. 61: 553556.
  • 28
    Jutel, M., Watanabe, T., Klunker, S., Akdis, M., Thomet, O. A., Malolepszy, J., Zak-Nejmark, T., et al., Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Nature 2001. 413: 420425.
  • 29
    Coyle, A. J., Wagner, K., Bertrand, C., Tsuyuki, S., Bews, J. and Heusser, C., Central role of immunoglobulin-E in the induction of lung eosinophil infiltration and T helper 2 cell cytokine production: Inhibition by a non-anaphylactogenic anti-IgE antibody. J. Exp. Med. 1996. 183: 13031308.
  • 30
    Akdis, C. A., Kussebi, F., Pulendran, B., Akdis, M., Lauener, R. P., Schmidt-Weber, C. B., Klunker, S., et al., Inhibition of T helper 2-type responses, IgE production and eosinophilia by synthetic lipopeptides. Eur. J. Immunol. 2003. 33: 27172726.
  • 31
    de Heer, H. J., Hammad, H., Soullie, T., Hijdra, D., Vos, N., Willart, M. A., Hoogsteden, H. C. and Lambrecht, B. N., Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J. Exp. Med. 2004. 200: 8998.
  • 32
    Markovic-Housley, Z., Miglierini, G., Soldatova, L., Rizkallah, P. J., Muller, U. and Schirmer, T., Crystal structure of hyaluronidase, a major allergen of bee venom. Structure Fold. Des. 2000. 8: 10251035.
  • 33
    Moser, M., Crameri, R., Menz, G., Schneider, T., Dudler, T., Virchow, C., Gmachl, M., et al., Cloning and expression of recombinant Aspergillus fumigatus allergen I/a (rAsp f I/a) with IgE binding and type I skin test activity. J. Immunol. 1992. 149: 454460.
  • 34
    Hemmann, S., Blaser, K. and Crameri, R., Allergens of Aspergillus fumigatus and Candida boidinii share IgE-binding epitopes. Am. J. Respir. Crit. Care Med. 1997. 156: 19561962.
  • 35
    Karamloo, F., Wangorsch, A., Kasahara, H., Davin, L. B., Haustein, D., Lewis, N. G. and Vieths, S., Phenylcoumaran benzylic ether and isoflavonoid reductases are a new class of cross-reactive allergens in birch pollen, fruits and vegetables. Eur. J. Biochem. 2001. 268: 53105320.
  • 36
    Cahen, Y. D., Maly, F. E. and Wuthrich, B., Cellular antigen stimulation test (CAST)-applicability in the diagnosis of insect toxin allergies. Schweiz. Med. Wochenschr. 1997. 127: 511.
  • 37
    Demoly, P., Bousquet, J., Manderscheid, J. C., Dreborg, S., Dhivert, H. and Michel, F. B., Precision of skin prick and puncture tests with nine methods. J. Allergy Clin. Immunol. 1991. 88: 758762.
  • 38
    Thomas, M. J., Noble, A., Sawicka, E., Askenase, P. W. and Kemeny, D. M., CD8 T cells inhibit IgE via dendritic cell IL-12 induction that promotes Th1 T cell counter-regulation. J. Immunol. 2002. 168: 216223.
  • 39
    Herrick, C. A., MacLeod, H., Glusac, E., Tigelaar, R. E. and Bottomly, K., Th2 responses induced by epicutaneous or inhalational protein exposure are differentially dependent on IL-4. J. Clin. Invest. 2000. 105: 765775.