t220 rBet v 4 Birch

Allergens within Tree Pollens

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  • Latin name: Betula verrucosa
  • Common names: 2 -EF-hand Ca2+-binding protein, polcalcin
  • Source material: Recombinant non-glycosylated protein produced in an E. coli strain carrying a cloned cDNA encoding Betula verrucosa allergen Bet v 4.
Recombinant allergen
Betula verrucosa allergen Bet v 4.
 
Biological function
Calcium-binding protein.
 
Mw
9.3 kDa.
 
Allergen description
Bet v 4 (1, 2-4), a calcium-binding protein (5-7), is a minor allergen in birch pollen that reacts with IgE antibodies from approximately 10-20% of pollen-sensitised subjects (2, 5, 8). Bet v 4 is a 9 kDa calcium-binding protein of 2-EF-hand type, which is represented in pollen of a wide range of plant species. It is 67-90% identical in amino acid sequence to homologous pollen proteins from Phleum pratense, Cynodon dactylon, Brassica rapa, Brassica napus, Olea europea and Alnus glutinosa (4, 9), and because of this extensive cross-reactivity can serve as a marker allergen for plant polysensitisation (10).
 
Bet v 3 and Bet v 4 have both been identified as EF-hand calcium-binding proteins primarily expressed in mature pollen (2, 4-5). Unlike Bet v 4, which contains only 2 calcium-binding domains. Bet v 3 is a 23.7 kDa protein containing 3 typical calcium-binding motifs (10).
 
It has been suggested that Bet v 1 can be a diagnostic marker allergen for identifying patients with genuine sensitisation to Birch-pollen (11), as opposed to patients reacting to highly cross-reactive allergens, such as Bet v 2 and Bet v 4; these may be considered marker allergens for syndromes involving cross-reactivity with numerous unrelated plants and plant products (12).
 
A study gives an example of the diagnostic application of recombinant birch pollen allergens. Serum IgE antibodies to Bet v 1, Bet v 2 and Bet v 4 were examined in birch-sensitive patients from the province of Cuneo, in northwest Italy. The study concluded that the 3 recombinant birch pollen allergens alone could identify 90% of Birch pollen-sensitive patients (1).


References:

    1. Rossi RE, Monasterolo G, Monasterolo S. Detection of specific IgE antibodies in the sera of patients allergic to birch pollen using recombinant allergens Bet v 1, Bet v 2, Bet v 4: evaluation of different IgE reactivity profiles. Allergy 2003 ;58(9):929-32.
    2. Twardosz A, Hayek B, Seiberler S, Vangelista L, Elfman L, Gronlund H, Kraft D, Valenta R. 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 1997;239(1):197-204.
    3. Ferreira F, Engel E, Briza P, Richter K, Ebner C, Breitenbach M. Characterization of recombinant Bet v 4, a birch pollen allergen with two EF-hand calcium-binding domains. Int Arch Allergy Immunol 1999;118(2-4):304-5.
    4. Engel E, Richter K, Obermeyer G, Briza P, Kungl AJ, et al. Immunological and biological properties of Bet v 4, a novel birch pollen allergen with two EF-hand calcium-binding domains. J Biol Chem 1997;272(45):28630-7.
    5. Seiberler S, Scheiner O, Kraft D, Lonsdale D, Valenta R. Characterization of a birch pollen allergen, Bet v III, 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 1994;13(15):3481-6.
    6. Neudecker P, Nerkamp J, Eisenmann A, Nourse A, Lauber T, Schweimer K, Lehmann K, Schwarzinger S, Ferreira F, Rosch P. Solution structure, dynamics, and hydrodynamics of the calcium-bound cross-reactive birch pollen allergen Bet v 4 reveal a canonical monomeric two EF-hand assembly with a regulatory function. J Mol Biol 2004;336(5):1141-57.
    7. Grote M, Hayek B, Reichelt R, Kraft D, Valenta R. Immunogold electron microscopic localization of the cross-reactive two-EF-hand calcium-binding birch pollen allergen Bet v 4 in dry and rehydrated birch pollen. Int Arch Allergy Immunol 1999;120(4):287-94.
    8. Karamloo F, Schmitz, N, Scheurer S, et al. Molecular cloning and characterization of a birch pollen minor allergen, Bet v 5, belonging to a family of isoflavone reductase-related proteins. J Allergy Clin Immunol 1999;104:991-999.
    9. Smith PM, Xu H, Swoboda I, Singh MB. 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 1997;114(3):265-71.
    10. Valenta R, Hayek B, Seiberler S, Bugajska-Schretter A, Niederberger V, Twardosz A, Natter S, Vangelista L, Pastore A, Spitzauer S, Kraft D. Calcium-binding allergens: from plants to man. Int Arch Allergy Immunol 1998;117(3):160-6.
    11. Kazemi-Shirazi L, Niederberger V, Linhart B, Lidholm J, Kraft D, Valenta R. Recombinant marker allergens: diagnostic gatekeepers for the treatment of allergy. Int Arch Allergy Immunol 2002;127(4):259-68.
    12. Mothes N, Valenta R. Biology of tree pollen allergens. Curr Allergy Asthma Rep 2004;4(5):384-90.

2006



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