Mimotopes identify conformational B-cell epitopes on the two major house dust mite allergens Der p 1 and Der p 2

Szalai, Krisztina; Fuhrmann, Jan; Pavkov, Tea; Scheidl, M; Wallmann, Julia; Brämswig, Kira H.; Vrtala, Susanne; Scheiner, Otto; Keller, Walter; Saint-Remy, Jean-Marie; Neumann, Dirk; Pali‐Schöll, Isabella; Jensen‐Jarolim, Erika

doi:10.1016/j.molimm.2007.09.012

Cited by 31 publications

(31 citation statements)

References 56 publications

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“…In another study, peptides with more than 30 amino acids were required for consistent antibody binding, which is in agreement with the importance of conformational epitopes for IgE binding to Der p 1 (24). Later on, phage display technology had been used to identify mimotopes from phage peptide libraries screened with antibodies specific for Der p 1 (26,27). Szalai et al .…”

Section: Discussionmentioning

confidence: 99%

Antigenic Determinants of Der p 1: Specificity and Cross-Reactivity Associated with IgE Antibody Recognition

Glesner

Vailes

Schlachter

et al. 2017

The Journal of Immunology

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Der p 1 and Der f 1 are major allergens from Dermatophagoides pteronyssinus and D. farinae, respectively. An analysis of antigenic determinants on both allergens was performed by site-directed mutagenesis. The analysis was based on the X-ray crystal structures of the allergens in complex with Fab fragments of three murine monoclonal antibodies that interfere with IgE antibody binding: the two Der p 1-specific mAb 5H8 and 10B9, and the cross-reactive mAb 4C1. On one hand, selected residues in the epitopes for mAb 5H8 and mAb 4C1 were substituted with amino acids that resulted in impaired antibody binding to Der p 1. On the other hand, an epitope for the Der p 1-specific mAb 10B9, which partially overlaps with mAb 4C1, was created in Der f 1. The mutation of 1–3 amino acid residues in Der f 1 was sufficient to bind mAb 10B9. These residues form hydrogen bonds with complementary determining regions (CDRs) of the Ab other than H CDR3. This observation enveils an exception to the dominant role of H CDR3 commonly observed in antigen recognition. Overall, this study resulted in the identification of important residues for mAb and IgE antibody recognition in group 1 mite allergens. This information can be used to engineer allergen mutants with reduced IgE antibody binding for immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Antigenic Determinants of Der p 1: Specificity and Cross-Reactivity Associated with IgE Antibody Recognition

Glesner

Vailes

Schlachter

et al. 2017

The Journal of Immunology

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“…Voraussetzung dafür ist die Kenntnis der Proteinstruktur des Allergens. Mit diesen Methoden wurden bereits Konformationsepitope verschiedenster Antigene aufgeklärt [13,[25][26][27][28].…”

Section: Mimotop-technologieunclassified

From the allergen-recognition by antibodies to new therapeutic concepts

Hantusch

Jensen‐Jarolim

2008

Wien Med Wochenschr

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Cross-linking of IgE antibodies through allergens is a basic event in type I allergy and leads to the immediate release of mediators like histamine, responsible for allergic symptoms like rhino-conjunctivitis or asthma. Critical for the binding of allergens to IgE are the IgE-epitopes, which represent a congregation of several amino acid residues often derived from different regions of the allergen. By means of the mimotope-technology, we isolated peptides from phage libraries, which were able to structurally mimic IgE-epitopes of the plant allergens Bet v 1 (birch) and Phl p 5a (timothy grass). Hence, these are candidates for an epitope-specific immunotherapy. In this mode of immunotherapy, it is the aim to induce IgG antibodies directed exclusively against the IgE-epitopes of allergens without induction of anaphylactogenic IgG species, and without the risk of anaphylaxis through cross-linking of IgE. Immunizing mice, we applied the mimotopes displayed on bacteriophages as well as on alternative carrier systems to enhance their antigenicity. With these systems it was possible to elicit an allergen-specific immune response, which was also accompanied by the appropriate T-cell help. Mimotopes resemble a promising concept for an epitope-tailored immunotherapy of allergic patients.

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“…An ideal vaccine for immunotherapy needs to preserve human IgG antibody-binding epitopes but to avoid human IgE antibody-binding sites [15,16]. Using mouse monoclonal or rabbit polyclonal antibodies, a number of antibody-binding epitopes have been disclosed for aeroallergens and food allergens [17,18,19,20,21,22,23]. We have previously characterized a sequential epitope (peptides 46–64) on Cyn d 1, the major allergen of BGP [24].…”

Section: Introductionmentioning

confidence: 99%

Mapping of IgE and IgG<sub>4</sub> Antibody-Binding Epitopes in Cyn d 1, the Major Allergen of Bermuda Grass Pollen

Yuan

Chen

et al. 2011

Int Arch Allergy Immunol

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Background: Bermuda grass pollen (BGP) is an important seasonal aeroallergen worldwide which induces allergic disorders such as allergic rhinitis, conjunctivitis and asthma. Cyn d 1 is the major allergen of BGP. This study is aimed to map human IgE and IgG₄ antibody-binding sequential epitopes on Cyn d 1 by dot immunoblotting. Methods: Synthetic peptides (10-mers; 5 overlapping residues) spanning the full length of Cyn d 1 were used for dot immunoblotting to map human IgE and IgG_1–4 antibody-binding regions with sera from BGP-allergic patients. Synthetic peptides with more overlapping residues were used for further mapping. Essential amino acids in each epitope were examined by single amino acid substitution with alanine. Peptides with sequence polymorphism of epitopes of Cyn d 1 were also synthesized to extrapolate their differences in binding capability. Results: Four major IgE-binding epitopes (peptides 15^–1, 21, 33^–2 and 35⁺¹, corresponding to amino acids 70–79, 101–110, 159–167 and 172–181) and 5 major IgG₄-binding epitopes (peptides 15^–1, 30^–2, 33^–2, 35⁺¹ and 39, corresponding to amino acids 70–79, 144–153, 159–167, 172–181 and 192–200) were identified. They are all located on the surface of the simulated Cyn d 1 molecule, and three of them are major epitopes for both IgE and IgG₄. Their critical amino acids were all characterized. Major epitopes for human IgG₁ to IgG₄ are almost identical. Conclusions: This is the first study to map the sequential epitopes for human IgE and IgG₄ subclasses in Cyn d 1. It will be helpful for future development in immunotherapy and diagnosis.

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Mimotopes identify conformational B-cell epitopes on the two major house dust mite allergens Der p 1 and Der p 2

Cited by 31 publications

References 56 publications

Antigenic Determinants of Der p 1: Specificity and Cross-Reactivity Associated with IgE Antibody Recognition

Antigenic Determinants of Der p 1: Specificity and Cross-Reactivity Associated with IgE Antibody Recognition

From the allergen-recognition by antibodies to new therapeutic concepts

Mapping of IgE and IgG<sub>4</sub> Antibody-Binding Epitopes in Cyn d 1, the Major Allergen of Bermuda Grass Pollen

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