Structural Analysis of Der p 1–Antibody Complexes and Comparison with Complexes of Proteins or Peptides with Monoclonal Antibodies

Osinski, T.; Pomés, Anna; Majorek, K.A.; Glesner, Jill; Offermann, L.R.; Vailes, Lisa D.; Chapman, Martin D.; Minor, Władek; Chruszcz, M.

doi:10.4049/jimmunol.1402199

Cited by 27 publications

(44 citation statements)

References 60 publications

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“…The group 1 allergens, Der p 1 and Der f 1, are cysteine proteases. The structures of natural Der p 1 and Der f 1 were determined, alone or in complex with fragments of monoclonal antibodies (mAb) that inhibit IgE antibody binding [8, 9, 10••] (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

“…Allergens fused to viral domains or viral-like particles have shown immunomodulatory capacity [21]. Another strategy is to perform site-directed mutagenesis of known IgE epitopes, based on the X-ray crystal structures of the allergens alone or in complex with monoclonal antibodies that interfere with IgE antibody binding [9, 10••, 32, 34, 35•, 123, 124]. …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Indoor Allergens and Allergic Respiratory Disease

Pomés

Chapman

Wünschmann

2016

Curr Allergy Asthma Rep

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Purpose of review The purpose of this review is to evaluate the most recent findings on indoor allergens and their impact on allergic diseases. Recent findings Indoor allergens are present inside buildings (home, work environment, school), and given the chronic nature of the exposures, indoor allergies tend to be associated with the development of asthma. The most common indoor allergens are derived from dust mites, cockroaches, mammals (including wild rodents and pets), and fungi. The advent of molecular biology and proteomics has led to the identification, cloning, and expression of new indoor allergens, which have facilitated research to elucidate their role in allergic diseases. This review is an update on new allergens and their molecular features, together with the most recent reports on their avoidance for allergy prevention and their use for diagnosis and treatment. Summary Research progress on indoor allergens will result in the development of new diagnostic tools and design of coherent strategies for immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Indoor Allergens and Allergic Respiratory Disease

Pomés

Chapman

Wünschmann

2016

Curr Allergy Asthma Rep

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“…84,85 The X-ray crystal structures of additional complexes revealed determinants of specificity and cross-reactivity. 47,86–91 Bla g 2 and Der p 1 have been extensively analyzed through the structures of two and four allergen-antibody complexes, respectively (Fig. 3E, F).…”

Section: How Crystallography Contributes To Clinical Practicementioning

confidence: 99%

“…3E, F). 47,89–91 The structural basis of cross-reactivity was analyzed for mAb 4C1, which binds Der p 1 and Der f 1 in equivalent epitopes (Fig. 3F).…”

Section: How Crystallography Contributes To Clinical Practicementioning

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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“…First, the structures of complexes of Der p 1 or Der f 1 with the cross-reactive mAb 4C1 revealed a common epitope between both allergens (9). Recently, the structures of the Der p 1-specific epitopes for mAb 5H8 and 10B9 were determined (10). Epitopes comprise a limited number of amino-acids forming different kinds of interactions with the antibody (hydrogen bonds, cation-π interactions, hydrophobic interactions, etc.).…”

Section: Introductionmentioning

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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Structural Analysis of Der p 1–Antibody Complexes and Comparison with Complexes of Proteins or Peptides with Monoclonal Antibodies

Cited by 27 publications

References 60 publications

Indoor Allergens and Allergic Respiratory Disease

Indoor Allergens and Allergic Respiratory Disease

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

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

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