Reshaping the Bet v 1 fold modulates TH polarization

Wallner, Michael; Hauser, Michael; Himly, Martin; Zaborsky, Nadja; Mutschlechner, Sonja; Harrer, Andrea; Asam, Claudia; Pichler, Ulrike; Ree, Ronald van; Briza, Peter; Thalhamer, Josef; Bohle, Barbara; Achatz, Gernot; Ferreira, Fátima

doi:10.1016/j.jaci.2011.01.064

Cited by 50 publications

(98 citation statements)

References 28 publications

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“…In silico screening of point mutations of Bet v 1 and Phl p 5 demonstrated similar results and in addition immunization with the hypoallergenic mutants produced antibodies that blocked human IgE epitopes [47]. Another computer analysis suggested a chimera of Bet v 1 and Mal d 1 would disrupt the fold of Bet v 1, which did result in a shift of the immune polarization compared to the wild type Bet v 1 [48]. These destabilizing predictions appear promising and it is notable that all of these examples did not require specific information about the patient epitopes, just the allergen structure [45].…”

Section: Immunotherapymentioning

confidence: 94%

Contributions and Future Directions for Structural Biology in the Study of Allergens

Mueller¹

2017

Int Arch Allergy Immunol

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Allergy is defined as an inappropriate immune response to something normally considered harmless. The symptomatic immune response is driven by IgE antibodies directed against allergens. The study of allergens has contributed significantly to our understanding of allergic disease in 3 main areas. First, identifying allergens as the cause of symptoms and developing allergen standards has led to many advances in exposure assessment and patient diagnostics. Second, a biochemical understanding of allergens has suggested a number of hypotheses related to the mechanisms of allergic sensitization. And finally, studies of allergen-antibody interactions have contributed to understanding the cross-reactivity of allergens, mapping patient epitopes, and the development of hypoallergens. In this review, a few select cases are highlighted where structural biology, in particular, has contributed significantly to allergen research and provided new avenues for investigation.

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Section: Immunotherapymentioning

confidence: 94%

Contributions and Future Directions for Structural Biology in the Study of Allergens

Mueller¹

2017

Int Arch Allergy Immunol

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“…Two amino acid positions in the egg-white allergen Gal d 1 have been identified as crucial for IgE binding as they contribute substantially to the structural integrity of the protein [100]. Sequence and fold analysis of members of the Bet v 1 family identified a short sequence stretch in Bet v 1, susceptible for mutations to induce an altered fold of the entire molecule [101]. The replacement of 7 consecutive amino acids of Bet v 1 by the homologous Mal d 1 sequence resulted in the loss of the Bet v 1-like fold and a drastic reduction in binding IgE in birch pollen-allergic individuals.…”

Section: Vaccine Developmentmentioning

confidence: 99%

Recombinant Allergens in Structural Biology, Diagnosis, and Immunotherapy

Tscheppe

Breiteneder²

2017

Int Arch Allergy Immunol

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The years 1988-1995 witnessed the beginning of allergen cloning and the generation of recombinant allergens, which opened up new avenues for the diagnosis and research of human allergic diseases. Most crystal and solution structures of allergens have been obtained using recombinant allergens. Structural information on allergens allows insights into their evolutionary biology, illustrates clinically observed cross-reactivities, and makes the design of hypoallergenic derivatives for allergy vaccines possible. Recombinant allergens are widely used in molecule-based allergy diagnosis such as protein microarrays or suspension arrays. Recombinant technologies have been used to produce well-characterized, noncontaminated vaccine components with known biological activities including a variety of allergen derivatives with reduced IgE reactivity. Such recombinant hypoallergens as well as wild-type recombinant allergens have been used successfully in several immunotherapy trials for more than a decade to treat birch and grass pollen allergy. As a more recent application, the development of antibody repertoires directed against conformational epitopes during immunotherapy has been monitored by recombinant allergen chimeras. Although much progress has been made, the number and quality of recombinant allergens will undoubtedly increase and keep improving our knowledge in basic scientific investigations, diagnosis, and therapy of human allergic diseases.

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“…Interestingly, the fold of Bet v 1.0101 per se was demonstrated to be important for Th2 polarization and the induction of a strong IgE response, by comparison with an engineered folding variant. 41 …”

Section: Allergen Structure As a Determinant Of Allergic Diseasementioning

confidence: 99%

100 Years later: Celebrating the contributions of x-ray crystallography to allergy and clinical immunology

Pomés

Chruszcz

Gustchina

et al. 2015

Journal of Allergy and Clinical Immunology

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Current knowledge of molecules involved in immunology and allergic disease results from significant contributions of X-ray crystallography, a discipline that just celebrated its 100th anniversary. The histories of allergens and X-ray crystallography are intimately intertwined. The first enzyme structure to be determined was lysozyme, also known as the chicken food allergen Gal d 4. Crystallography determines the exact three-dimensional positions of atoms in molecules. Structures of molecular complexes in the disciplines of immunology and allergy have revealed the atoms involved in molecular interactions and in mechanisms of disease. These complexes include peptides presented by MHC class II molecules, cytokines bound to their receptors, allergen-antibody complexes, and innate immune receptors with their ligands. The information derived from crystallographic studies provides insights into the function of molecules. Allergen function is one of the determinants of environmental exposure, which is essential for IgE sensitization. Proteolytic activity of allergens or their capacity to bind lipopolysaccharides may also contribute to allergenicity. The atomic positions define the molecular surface that is accessible to antibodies. This surface in turn determines antibody specificity and cross-reactivity that are important factors for the selection of allergen panels used for molecular diagnosis and for the interpretation of clinical symptoms. This review celebrates the contributions of X-ray crystallography to clinical immunology and allergy, focusing on new molecular perspectives that influence the diagnosis and treatment of allergic diseases.

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Reshaping the Bet v 1 fold modulates TH polarization

Cited by 50 publications

References 28 publications

Contributions and Future Directions for Structural Biology in the Study of Allergens

Contributions and Future Directions for Structural Biology in the Study of Allergens

Recombinant Allergens in Structural Biology, Diagnosis, and Immunotherapy

100 Years later: Celebrating the contributions of x-ray crystallography to allergy and clinical immunology

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