Recombinant birch pollen allergens (rBet v 1 and rBet v 2) contain most of the IgE epitopes present in birch, alder, hornbeam, hazel, and oak pollen: A quantitative IgE inhibition study with sera from different populations☆☆☆★★★

Niederberger, Verena; Pauli, G.; Grönlundc, Hans; Fröschla, Renate; Rumpold, Helmut; Kraft, Dietrich; Valenta, Rudolf; Spitzauer, Susanne

doi:10.1016/s0091-6749(98)70273-8

Cited by 191 publications

(178 citation statements)

References 51 publications

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“…Detection of binding of birch pollen profilin-specific IgE to reactive epitopes in PVDF membrane-bound recombinant birch profilin was performed as previously described (5,(17)(18)(19). Briefly, native or ␣-chymasecleaved purified recombinant birch profilin (BIOMAY) was electrophoresed onto 12% bis-Tris polyacrylamide gels and transferred to PVDF as described above.…”

Section: Ige Immunoblottingmentioning

confidence: 99%

“…The use of control serum from nonallergic individuals establishes the specificity of the binding of IgE present in allergic serum, while preadsorption of allergic sera with purified allergens in IgE inhibition experiments may identify cross-sensitization of individuals to allergens in unrelated trees, weeds, or grasses (5,(17)(18)(19). To determine the effect of ␣-chymase hydrolysis of birch profilin on binding of allergenspecific IgE, immunoblotting of native or ␣-chymase-cleaved birch profilin was performed using serum from individuals allergic to birch pollen.…”

Section: Ige Immunoblotmentioning

confidence: 99%

“…Individuals exhibiting allergic responses to birch pollen very frequently raise IgE Abs to a specific protein, Bet v 2, otherwise known as profilin. These Abs tend to cross-react extensively with a broad range of other plant profilins (5). Challenge of allergic patients with birch pollen redistributes mast cells toward the nasal mucosa (2), induces mast cell chemotactic activity (6), and increases histamine and tryptase levels in nasal lavage fluid (1).…”

mentioning

confidence: 99%

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Mast Cell α-Chymase Reduces IgE Recognition of Birch Pollen Profilin by Cleaving Antibody-Binding Epitopes

Mellon

Frank

Fang

2002

The Journal of Immunology

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In sensitized individuals birch pollen induces an allergic response characterized by IgE-dependent mast cell degranulation of mediators, such as α-chymase and other serine proteases. In birch and other plant pollens, a major allergen is profilin. In mammals, profilin homologues are found in an intracellular form bound to cytoskeletal or cytosolic proteins or in a secreted form that may initiate signal transduction. IgE specific to birch profilin also binds human profilin I. This cross-reactivity between airborne and endogenous proteins may help to sustain allergy symptoms. The current work demonstrates that cultured mast cells constitutively secrete profilin I, which is susceptible to degranulation-dependent proteolysis. Coincubation of chymase-rich BR mastocytoma cells with Ala-Ala-Pro-Phe-chloromethylketone (a chymase inhibitor) blocks profilin cleavage, which does not occur in degranulated HMC-1 mast cells, which are rich in tryptase, but chymase deficient. These data implicate chymase as the serine protease cleaving secreted mast cell profilin. Sequencing of chymase-cleaved profilins reveals hydrolysis at Tyr6-Val7 and Trp35-Ala36 in birch profilin and at Trp32-Ala33 in human profilin, with all sites lying within IgE-reactive epitopes. IgE immunoblotting studies with sera from birch pollen-allergic individuals demonstrate that cleavage by chymase attenuates binding of birch profilin to IgE. Thus, destruction of IgE-binding epitopes by exocytosed chymase may limit further mast cell activation by this class of common plant allergens, thereby limiting the allergic responses in sensitized individuals.

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Section: Ige Immunoblottingmentioning

confidence: 99%

Section: Ige Immunoblotmentioning

confidence: 99%

mentioning

confidence: 99%

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Mast Cell α-Chymase Reduces IgE Recognition of Birch Pollen Profilin by Cleaving Antibody-Binding Epitopes

Mellon

Frank

Fang

2002

The Journal of Immunology

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“…In addition, sera were screened for the presence of IgE Abs to birch pollen extract by radio allergosorbent test (RAST) (Pharmacia, Uppsala, Sweden) and by IgE immunoblotting as described (21).…”

Section: Patients' Sera Plasmid Vectors E Coli Strains and Recombmentioning

confidence: 99%

“…Bet v 1 is recognized by Ͼ95% of birch pollen allergic patients, and 60% of these patients react exclusively with this allergen (17,18). The cDNA coding for Bet v 1 was isolated (19), and recombinant Bet v 1, which has immunological and biological properties comparable to natural Bet v 1 (18,20) and shares epitopes with homologous proteins present in the pollen of trees of the order Fagales and in plant-derived food was produced in Escherichia coli (21)(22)(23)(24). When analyzed by circular dichroism spectroscopy, the bacterially expressed rBet v 1 wild-type molecule was folded and consisted of mixed ␣ helical and ␤-sheet conformation (25,26).…”

mentioning

confidence: 99%

T Cell Epitope-Containing Hypoallergenic Recombinant Fragments of the Major Birch Pollen Allergen, Bet v 1, Induce Blocking Antibodies

Vrtala

Akdiş²,

Budak³

et al. 2000

The Journal of Immunology

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Allergen-specific immunotherapy represents one of the few curative approaches toward type I allergy. Up to 25% of allergic patients are sensitized against the major birch pollen allergen, Bet v 1. By genetic engineering we produced two recombinant (r) Bet v 1 fragments comprising aa 1–74 and aa 75–160 of Bet v 1, which, due to a loss of their native-like fold, failed to bind IgE Abs and had reduced allergenic activity. Here we show that both fragments covering the full Bet v 1 sequence induced human lymphoproliferative responses similar to rBet v 1 wild type. The C-terminal rBet v 1 fragment induced higher lymphoproliferative responses than the N-terminal fragment and represented a Th1-stimulating segment with high IFN-γ production, whereas the N-terminal fragment induced higher IL-4, IL-5, and IL-13 secretion. Immunization of mice and rabbits with rBet v 1 fragments induced IgG Abs, which cross-reacted with complete Bet v 1 and Bet v 1-related plant allergens and strongly inhibited the IgE binding of allergic patients to these allergens. Thus, our results demonstrate that hypoallergenic T cell epitope-containing rBet v 1 fragments, despite lacking IgE epitopes, can induce Abs in vivo that prevent the IgE binding of allergic patients to the wild-type allergen. The overall demonstration of the immunogenic features of the hypoallergenic rBet v 1 fragments will now enable clinical studies for safer and more efficient specific immunotherapy.

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Evolution of IgM, IgE and IgG1-4antibody responses in early childhood monitored with recombinant allergen components: implications for class switch mechanisms

et al. 2002

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The formation of IgE antibodies against environmental allergens represents the hallmark of type I allergy. Data from in vitro cultured cells and experimental animal models provide controversial evidence for isotype switching from IgM to IgE production via sequential as well as non‐sequential (i.e. direct) class switch. We analyzed the evolution of IgE responses in 11 children developing birch pollen and/or grass pollen allergy during the first 7 years of life using purified recombinant allergen molecules (major birch pollen allergen, Bet v 1; major timothy grass pollen allergens, Phl p 1, Phl p 2, Phl p 5). Demographic, clinical and serological data indicated a postnatal sensitization to pollen allergens. A parallel development of IgG1–4 and IgE responses to recombinant allergen molecules compatible with a strictly sequential class switch to IgE was observed only in one child. The only partly synchronized and dissociated development of allergen‐specific antibody responses found in all other cases can be best explained by a partly sequential class switch involving few switch stations or, more likely, by direct class switching. Kinetics and courses of allergen‐specific antibody responses (IgM, IgG1–4, IgE) during the first years of life suggest that, once established, allergen‐specific IgE responses are driven by antigen contact rather than by cytokines controlling class switch to IgE.

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Recombinant birch pollen allergens (rBet v 1 and rBet v 2) contain most of the IgE epitopes present in birch, alder, hornbeam, hazel, and oak pollen: A quantitative IgE inhibition study with sera from different populations☆☆☆★★★

Cited by 191 publications

References 51 publications

Mast Cell α-Chymase Reduces IgE Recognition of Birch Pollen Profilin by Cleaving Antibody-Binding Epitopes

Mast Cell α-Chymase Reduces IgE Recognition of Birch Pollen Profilin by Cleaving Antibody-Binding Epitopes

T Cell Epitope-Containing Hypoallergenic Recombinant Fragments of the Major Birch Pollen Allergen, Bet v 1, Induce Blocking Antibodies

Evolution of IgM, IgE and IgG1-4antibody responses in early childhood monitored with recombinant allergen components: implications for class switch mechanisms

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