Abstract
AbstractSerum IgE was used to isolate a cDNA coding for a 9.4-kDa two EF-hand calcium-binding allergen, Aln g 4, from a λgt11 expression cDNA library constructed from alder (Alnus glutinosa) pollen. rAln g 4 was overexpressed in Escherichia coliand purified to homogeneity. It reacted with serum IgE from 18% of pollen-allergic patients (n = 122); shared IgE epitopes with homologous allergens present in tree, grass, and weed pollens; and thus belongs to a family of highly cross-reactive pollen allergens. Exposure of two E. coli-expressed rAln g 4 fragments comprising amino acids 1–41 and 42–85 to patients’ IgE Abs, as well as to a rabbit antiserum raised against purified rAln g 4, indicated that most of the B cell epitopes reside in the N-terminal portion of the protein. IgE recognition of Aln g 4 was strongly modulated by the presence or absence of calcium. Circular dichroism analysis of rAln g 4 revealed that the protein consisted mostly of α helical secondary structure and possessed a remarkable thermal stability and refolding capacity, a property that was greatly reduced after calcium depletion. Circular dichroism analysis of the calcium-bound and apo form of rAln g 4 indicated that calcium-induced modulation of IgE binding could be due to changes in the protein conformation. Purified rAln g 4 elicited dose-dependent basophil histamine release and immediate type skin reactions in sensitized patients. It may hence be useful for allergy diagnosis and for specific immunotherapy.
Bibliography
Hayek, B., Vangelista, L., Pastore, A., Sperr, W. R., Valent, P., Vrtala, S., Niederberger, V., Twardosz, A., Kraft, D., & Valenta, R. (1998). Molecular and Immunologic Characterization of a Highly Cross-Reactive Two EF-Hand Calcium-Binding Alder Pollen Allergen, Aln g 4: Structural Basis for Calcium-Modulated IgE Recognition. The Journal of Immunology, 161(12), 7031â7039.
References
56
Referenced
58
- Kay, A. B.. 1997. Allergy and Allergic Diseases Blackwell Science, Oxford.
-
Casolaro, V., S. N. Georas, Z. Song, S. J. Ono. 1996. Biology and genetics of atopic disease. Curr. Opin. Immunol. 8: 796
(
10.1016/S0952-7915(96)80007-0
) -
Segal, D. M., J. D. Taurog, H. Metzger. 1977. Dimeric immunoglobulin E serves as a unit signal for mast cell degranulation. Proc. Natl. Acad. Sci. USA 74: 2993
(
10.1073/pnas.74.7.2993
) -
R. F. Lockey, and E. Fernandez-Caldas, and S. C. Bukantz, eds. Allergens and Allergen Immunotherapy 2nd Ed.1998 Marcel Dekker, New York.
(
10.1201/9780824752514
) -
Grote, M., S. Vrtala, R. Valenta. 1993. Monitoring of two allergens, Bet v 1 and profilin, in dry and rehydrated birch pollen by immunogold electron microscopy and immunoblotting. J. Histochem. Cytochem. 41: 745
(
10.1177/41.5.8468456
) -
Grote, M., C. Dolecek, R. vanRee, R. Valenta. 1994. Immunogold electron microscopic localization of timothy grass (Phleum pratense) pollen major allergens Phl p 1 and Phl p 5 after anhydrous fixation in acrolein vapor. J. Histochem. Cytochem. 42: 427
(
10.1177/42.3.8308259
) -
Grote, M., P. Wiedemann, S. Lebecque, R. Valenta. 1998. Human monoclonal IgG antibodies derived from a patient allergic to birch pollen as tools to study the in situ localization of the major birch pollen allergen, Bet v 1, by immunogold electron microscopy. J. Allergy Clin. Immunol. 101: 60
(
10.1016/S0091-6749(98)70194-0
) -
Grote, M., S. Fischer, W. D. Müller, R. Valenta. 1998. In situ localization of a high molecular weight cross-reactive allergen in pollen and plant-derived food by immunogold electron microscopy. J. Allergy Clin. Immunol. 101: 250
(
10.1016/S0091-6749(98)70390-2
) -
Vrtala, S., M. Grote, M. Duchêne, R. vanRee, D. Kraft, O. Scheiner, R. Valenta. 1993. Properties of tree and grass pollen allergens; reinvestigation of the linkage between solubility and allergenicity. Int. Arch. Allergy Immunol. 102: 160
(
10.1159/000236567
) -
Suphioglu, C., M. B. Singh, P. Taylor, R. Bellomo, P. Holmes, R. Puy, R. B. Knox. 1992. Mechanism of grass-pollen-induced asthma. Lancet 339: 569
(
10.1016/0140-6736(92)90864-Y
) -
Valenta, R., D. Kraft. 1995. Recombinant allergens for diagnosis and therapy of allergic diseases. Curr. Opin. Immunol. 7: 751
(
10.1016/0952-7915(95)80043-3
) -
Valenta, R., S. Vrtala, S. Laffer, S. Spitzauer, D. Kraft. 1998. Recombinant allergens. Allergy 53: 552
(
10.1111/j.1398-9995.1998.tb03930.x
) -
Perez, M., G. Y. Ishioka, L. E. Walker, R. W. Chestnut. 1990. cDNA cloning and immunological characterization of the rye grass allergen Lol p I. J. Biol. Chem. 265: 16210
(
10.1016/S0021-9258(17)46209-0
) -
Laffer, S., R. Valenta, S. Vrtala, M. Susani, R. vanRee, D. Kraft, O. Scheiner, M. Duchêne. 1994. Complementary DNA cloning of the major allergen Phl p I from timothy grass (Phleum pratense); recombinant Phl p I inhibits IgE-binding to group I allergens from eight different grass species. J. Allergy Clin. Immunol. 94: 689
(
10.1016/0091-6749(94)90176-7
) -
Sidoli, A., E. Tamborini, I. Giuntini, S. Levi, G. Volonte, C. Paini, C. De Lalla, A. G. Siccardi, F. E. Baralle, S. Galliani, P. Arosio. 1993. Cloning, expression and immunological characterization of recombinant Lolium perenne allergen Lol p II. J. Biol. Chem. 268: 21819
(
10.1016/S0021-9258(20)80615-2
) -
Dolecek, C., S. Vrtala, S. Laffer, P. Steinberger, D. Kraft, O. Scheiner, R. Valenta. 1993. Molecular characterization of Phl p II, a major timothy grass (Phleum pratense) pollen allergen. FEBS Lett. 335: 299
(
10.1016/0014-5793(93)80406-K
) -
Silvanovic, A., J. Astwood, L. Zhang, E. Olsen, F. Kisil, A. Sehon, S. Mohapatra, R. Hill. 1991. Nucleotide sequence analysis of three cDNAs coding for Poa p IX isoallergens of Kentucky bluegrass pollen. J. Biol. Chem. 266: 1204
(
10.1016/S0021-9258(17)35302-4
) -
Singh, M. B., T. Hough, P. Theerakulipsut, A. Avjioglu, S. Davies, P. M. Smith, P. Taylor, R. J. Simpson, L. D. Ward, J. McCluskey, R. Puy, B. Knox. 1991. Isolation of cDNA encoding a newly identified major allergenic protein of rye-grass pollen: intracellular targeting to the amyloplast. Proc. Natl. Acad. Sci. USA 88: 1384
(
10.1073/pnas.88.4.1384
) -
Vrtala, S., W. R. Sperr, I. Reimitzer, R. vanRee, S. Laffer, W. D. Müller, P. Valent, K. Lechner, H. Rumpold, D. Kraft, O. Scheiner, R. Valenta. 1993. cDNA cloning of a major allergen from timothy grass (Phleum pratense) pollen: characterization of the recombinant Phl p V allergen. J. Immunol. 151: 4773
(
10.4049/jimmunol.151.9.4773
) -
Petersen, A., A. Bufe, G. Schramm, M. Schlaak, W. M. Becker. 1995. Characterization of the allergen group VI in timothy grass pollen (Phl p 6). II. cDNA cloning of Phl p 6 and structural comparison to grass group V. Int. Arch. Allergy Immunol. 108: 55
(
10.1159/000237118
) -
Valenta, R., M. Duchêne, C. Ebner, P. Valent, C. Sillaber, P. Deviller, F. Ferreira, M. Tejkl, H. Edelmann, D. Kraft, O. Scheiner. 1992. Profilins constitute a novel family of functional plant pan-allergens. J. Exp. Med. 175: 377
(
10.1084/jem.175.2.377
) -
VanRee, R., V. Voitenko, W. A. vanLeeuwen, R. C. Aalberse. 1992. Profilin is a cross-reactive allergen in pollen and vegetable food. Int. Arch. Allergy Immunol. 98: 97
(
10.1159/000236171
) -
Ebner, C., R. Hirschwehr, L. Bauer, H. Breiteneder, R. Valenta, H. Ebner, D. Kraft, O. Scheiner. 1995. Identification of allergens in fruits and vegetables: IgE cross-reactivities with the important birch pollen allergens Bet v 1 and Bet v 2 (birch profilin). J. Allergy Clin. Immunol. 95: 962
(
10.1016/S0091-6749(95)70096-X
) -
Jensen-Jarolim, E., A. Leitner, R. Hirschwehr, D. Kraft, B. Wüthrich, O. Scheiner. 1997. Characterization of allergens in Apicaceae spices: anise, fennel, coriander and cumin. Clin. Exp. Allergy 27: 1299
(
10.1046/j.1365-2222.1997.1580956.x
) -
Vallier, P., S. Balland, R. Harf, R. Valenta, P. Deviller. 1995. Identification of profilin as an IgE-binding component in latex from Hevea brasiliensis: clinical implications. Clin. Exp. Allergy 25: 332
(
10.1111/j.1365-2222.1995.tb01051.x
) -
Fuchs, T., S. Spitzauer, C. Vente, J. Hevler, S. Kapiotis, H. Rumpold, D. Kraft, R. Valenta. 1997. Natural latex, grass pollen, and weed pollen share IgE epitopes. J. Allergy Clin. Immunol. 100: 356
(
10.1016/S0091-6749(97)70249-5
) -
Valenta, R., P. Steinberger, M. Duchêne, D. Kraft. 1996. Immunological and structural similarities among allergens: prerequisite for a specific and component-based therapy of allergy. Immunol. Cell Biol. 74: 187
(
10.1038/icb.1996.26
) -
Valenta, R., M. Duchêne, K. Pettenburger, C. Sillaber, P. Valent, P. Bettelheim, M. Breitenbach, H. Rumpold, D. Kraft, O. Scheiner. 1991. Identification of profilin as a novel pollen allergen; IgE autoreactivity in sensitized individuals. Science 253: 557
(
10.1126/science.1857985
) -
Valenta, R., F. Ferreira, M. Grote, I. Swoboda, S. Vrtala, M. Duchêne, P. Deviller, R. B. Meagher, E. McKinney, E. Heberle-Bors, D. Kraft, O. Scheiner. 1993. Identification of profilin as an actin binding protein in higher plants. J. Biol. Chem. 268: 22777
(
10.1016/S0021-9258(18)41594-3
) -
Fedorov, A. A., T. Ball, R. Valenta, S. C. Almo. 1997. The molecular basis for allergen cross-reactivity: crystal structure and IgE-epitope mapping of birch pollen profilin. Structure 5: 33
(
10.1016/S0969-2126(97)00164-0
) -
Breiteneder, H., K. Pettenburger, A. Bito, R. Valenta, D. Kraft, H. Rumpold, O. Scheiner, M. Breitenbach. 1989. The gene coding for the major birch pollen allergen, Bet v 1, is highly homologous to a pea disease resistance response gene. EMBO J. 8: 1935
(
10.1002/j.1460-2075.1989.tb03597.x
) -
Bufe, A., M. D. Spangfort, H. Kahlert, M. Schlaak, W. M. Becker. 1996. The major birch pollen allergen, Bet v 1, shows ribonuclease activity. Planta 199: 413
(
10.1007/BF00195733
) -
Niederberger, V., G. Pauli, H. Grönlund, R. Fröschl, H. Rumpold, D. Kraft, R. Valenta, and S. Spitzauer. 1998. Recombinant birch pollen allergens (rBet v 1, rBet v 2) contain most of the IgE epitopes present in birch, alder, hornbeam, hazel and oak pollen: a quantitative IgE inhibition study using sera from different populations. J. Allergy Clin. Immunol. In press.
(
10.1016/S0091-6749(98)70273-8
) -
Valenta, R., D. Kraft. 1996. Type I allergic reactions to plant-derived food: a consequence of primary sensitization to pollen allergens. J. Allergy Clin. Immunol. 97: 893
(
10.1016/S0091-6749(96)80062-5
) -
Seiberler, S., O. Scheiner, D. Kraft, R. Valenta. 1994. Characterization of a birch pollen allergen, Bet v 3, representing a novel class of Ca2+ binding proteins: specific expression in mature pollen and dependence of patients’ IgE binding on protein bound Ca2+. EMBO J. 13: 3481
(
10.1002/j.1460-2075.1994.tb06654.x
) -
Twardosz, A., B. Hayek, S. Seiberler, L. Vangelista, L. Elfman, H. Grönlund, D. Kraft, R. Valenta. 1997. Molecular characterization, expression in Escherichia coli, and epitope analysis of a two EF-hand calcium-binding birch pollen allergen, Bet v 4. Biochem. Biophys. Res. Commun. 239: 197
(
10.1006/bbrc.1997.6860
) -
Engel, E., K. Richter, G. Obermeyer, P. Briza, A. J. Kungl, B. Simon, M. Auer, C. Ebner, H. J. Rheinberger, M. Breitenbach, F. Ferreira. 1997. Immunological and biological properties of Bet v 4, a novel birch pollen allergen with two EF-hand calcium-binding domains. J. Biol. Chem. 272: 28630
(
10.1074/jbc.272.45.28630
) -
Smith, P. M., H. Xu, I. Swoboda, M. B. Singh. 1997. Identification of a Ca2+ binding protein as a new Bermuda grass pollen allergen Cyn d 7: IgE cross-reactivity with oilseed rape pollen allergen Bra r 1. Int. Arch. Allergy Immunol. 114: 265
(
10.1159/000237678
) -
Suphioglu, C., F. Ferreira, R. B. Knox. 1997. Molecular cloning and immunological characterization of Cyn d 7, a novel calcium-binding allergen from Bermuda grass pollen. FEBS Lett. 402: 167
(
10.1016/S0014-5793(96)01520-7
) -
Fling, S. P., D. S. Gregerson. 1986. Peptide and protein molecular weight determination by electrophoresis using a high molarity Tris buffer system without urea. Anal. Biochem. 155: 83
(
10.1016/0003-2697(86)90228-9
) -
Towbin, H., T. Staehelin, J. Gordon. 1979. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc. Natl. Acad. Sci. USA 76: 4350
(
10.1073/pnas.76.9.4350
) - Sambrook, J., E. F. Fritsch, T. Maniatis. 1989. Molecular Cloning: A Laboratory Manual Cold Spring Harbor Laboratory Press, Cold Spring Harbor.
-
Sanger, F., S. Nicklen, A. R. Coulson. 1977. DNA sequencing with chain-termination inhibitors. Proc. Natl. Acad. Sci. USA 74: 5463
(
10.1073/pnas.74.12.5463
) -
Valent, P., J. Besmer, M. Muhm, O. Maijdic, K. Lechner, P. Bettelheim. 1989. Interleukin 3 activates human blood basophils via high-affinity binding sites. Proc. Natl. Acad. Sci. USA 86: 5542
(
10.1073/pnas.86.14.5542
) -
Vrtala, S., K. Hirtenlehner, L. Vangelista, A. Pastore, H. G. Eichler, W. R. Sperr, P. Valent, C. Ebner, D. Kraft, R. Valenta. 1997. Conversion of the major birch pollen allergen, Bet v 1, into two nonanaphylactic T cell epitope containing fragments; candidates for a novel form of specific immunotherapy. J. Clin. Invest. 99: 1673
(
10.1172/JCI119330
) -
Breiteneder, H., K. Hoffmann-Sommergruber, C. Ebner, A. Reikerstorfer, M. Duchêne, F. Ferreira, R. Valenta, M. Breitenbach, D. Kraft, O. Scheiner. 1992. cDNA cloning and expression in Escherichia coli of Aln g I, the major allergen in pollen of alder (Alnus glutinosa). J. Allergy Clin. Immunol. 90: 909
(
10.1016/0091-6749(92)90463-C
) -
Herzberg, O., J. Moult, M. N. James. 1986. A model for the Ca2+-induced conformational transition of troponin C: a trigger for muscle contraction. J. Biol. Chem. 261: 2638
(
10.1016/S0021-9258(17)35835-0
) -
Toriyama, K., T. Okada, M. Watanabe, T. Ide, T. Ashida, H. Xu, M. B. Singh. 1995. A cDNA clone encoding an IgE-binding protein from Brassica anther has significant sequence similarity to Ca2+-binding proteins. Plant Mol. Biol. 29: 1157
(
10.1007/BF00020459
) -
Batanero, E., M. Villalba, A. Ledesma, X. S. Puente, R. Rodriguez. 1996. Ole e 3, an olive tree allergen, belongs to a widespread family of pollen proteins. Eur. J. Biochem. 241: 772
(
10.1111/j.1432-1033.1996.00772.x
) -
Kraulis, P.. 1991. MOLSCRIPT: a program to produce both detailed and schematic plots of protein structures. J. Appl. Crystallogr. 24: 946
(
10.1107/S0021889891004399
) -
Dayringer, H. E., A. Tramontano, S. Sprang, R. J. Fletterick. 1986. INSIGHT: an interactive molecular graphics package. J. Mol. Graph. 4: 82
(
10.1016/0263-7855(86)80002-9
) -
Menz, G., C. Dolecek, U. Schönheit-Kenn, F. Ferreira, M. Moser, T. Schneider, M. Suter, G. Boltz-Nitulescu, C. Ebner, D. Kraft, R. Valenta. 1996. Serological and skin-test diagnosis of birch pollen allergy with recombinant Bet v 1, the major birch pollen allergen. Clin. Exp. Allergy 26: 50
(
10.1111/j.1365-2222.1996.tb00056.x
) -
Pauli, G., J. Oster, P. Deviller, S. Heiss, J. Bessot, M. Susani, F. Ferreira, D. Kraft, R. Valenta. 1996. Skin testing with recombinant allergens rBet v 1 and rBet v 2: diagnostic value for birch pollen and associated allergies. J. Allergy Clin. Immunol. 97: 1100
(
10.1016/S0091-6749(96)70264-6
) - Kawasaki, H., R. H. Kretsinger. 1994. Calcium-binding proteins. Protein Profile 343 Academic Press, San Diego.
-
Ikura, M.. 1996. Calcium binding and conformational response in EF-hand proteins. Trends Biochem. Sci. 21: 14
(
10.1016/S0968-0004(06)80021-6
) -
Bugajska-Schretter, A., L. Elfman, S. Kapiotis, H. Rumpold, R. Valenta, S. Spitzauer. 1998. Parvalbumin, a cross-reactive fish allergen contains IgE epitopes sensitive to periodate treatment and Ca2+ depletion. J. Allergy Clin. Immunol. 101: 67
(
10.1016/S0091-6749(98)70195-2
)
Dates
Type | When |
---|---|
Created | 2 years, 8 months ago (Dec. 30, 2022, 12:40 p.m.) |
Deposited | 7 months, 4 weeks ago (Jan. 2, 2025, 1:09 p.m.) |
Indexed | 3 months, 2 weeks ago (May 17, 2025, 2:47 a.m.) |
Issued | 26 years, 8 months ago (Dec. 15, 1998) |
Published | 26 years, 8 months ago (Dec. 15, 1998) |
Published Print | 26 years, 8 months ago (Dec. 15, 1998) |
@article{Hayek_1998, title={Molecular and Immunologic Characterization of a Highly Cross-Reactive Two EF-Hand Calcium-Binding Alder Pollen Allergen, Aln g 4: Structural Basis for Calcium-Modulated IgE Recognition}, volume={161}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.161.12.7031}, DOI={10.4049/jimmunol.161.12.7031}, number={12}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Hayek, Brigitte and Vangelista, Luca and Pastore, Annalisa and Sperr, Wolfgang R. and Valent, Peter and Vrtala, Susanne and Niederberger, Verena and Twardosz, Anna and Kraft, Dietrich and Valenta, Rudolf}, year={1998}, month=dec, pages={7031–7039} }