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Molecular determinants for antibody binding on group 1 house dust mite allergens.

ABSTRACT: House dust mites produce potent allergens, Der p 1 and Der f 1, that cause allergic sensitization and asthma. Der p 1 and Der f 1 are cysteine proteases that elicit IgE responses in 80% of mite-allergic subjects and have proinflammatory properties. Their antigenic structure is unknown. Here, we present crystal structures of natural Der p 1 and Der f 1 in complex with a monoclonal antibody, 4C1, which binds to a unique cross-reactive epitope on both allergens associated with IgE recognition. The 4C1 epitope is formed by almost identical amino acid sequences and contact residues. Mutations of the contact residues abrogate mAb 4C1 binding and reduce IgE antibody binding. These surface-exposed residues are molecular targets that can be exploited for development of recombinant allergen vaccines.

SUBMITTER: Chruszcz M

PROVIDER: S-EPMC3293536 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Molecular determinants for antibody binding on group 1 house dust mite allergens.

Chruszcz Maksymilian M Pomés Anna A Glesner Jill J Vailes Lisa D LD Osinski Tomasz T Porebski Przemyslaw J PJ Majorek Karolina A KA Heymann Peter W PW Platts-Mills Thomas A E TA Minor Wladek W Chapman Martin D MD

The Journal of biological chemistry 20111230 10

House dust mites produce potent allergens, Der p 1 and Der f 1, that cause allergic sensitization and asthma. Der p 1 and Der f 1 are cysteine proteases that elicit IgE responses in 80% of mite-allergic subjects and have proinflammatory properties. Their antigenic structure is unknown. Here, we present crystal structures of natural Der p 1 and Der f 1 in complex with a monoclonal antibody, 4C1, which binds to a unique cross-reactive epitope on both allergens associated with IgE recognition. The ...[more]

PMID: 22210776

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Characterization of a serine protease homologous to house dust mite group 3 allergens from the scabies mite Sarcoptes scabiei.

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Cellular and Molecular Events in the Airway Epithelium Defining the Interaction Between House Dust Mite Group 1 Allergens and Innate Defences.

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Allergen Delivery Inhibitors: A Rationale for Targeting Sentinel Innate Immune Signaling of Group 1 House Dust Mite Allergens through Structure-Based Protease Inhibitor Design.

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| S-EPMC6064784 | biostudies-literature

The SQ House Dust Mite SLIT-Tablet Is Well Tolerated in Patients with House Dust Mite Respiratory Allergic Disease.

Project description:BackgroundThe SQ house dust mite (HDM) SLIT-tablet (ALK, Denmark) addresses the underlying cause of HDM respiratory allergic disease, and a clinical effect has been demonstrated for both HDM allergic rhinitis and allergic asthma. Here, we present pooled safety data from an adult population with HDM respiratory allergy, with particular focus on the impact of asthma on the SQ HDM SLIT-tablet tolerability profile.MethodsSafety data from 2 randomised double-blind, placebo-controlled clinical trials were included: MT-04: 834 adults with HDM allergic asthma not well controlled by inhaled corticosteroids and with HDM allergic rhinitis, and MT-06: 992 adults with moderate-to-severe HDM allergic rhinitis despite the use of allergy pharmacotherapy and with or without asthma.ResultsThe proportion of subjects experiencing adverse events (AEs) was greater in the active treatment group (12 SQ-HDM; 73% of subjects) compared to placebo (53%). The most common treatment-related AEs were local allergic reactions. No AEs were reported as systemic allergic reactions. Regardless of asthma status, most AEs were mild or moderate (>97% of AEs) and the frequency of serious AEs was low. Subgroup analysis revealed no statistically significant difference in the risk of experiencing moderate or severe treatment-related AEs for subjects with asthma compared to subjects without asthma (p = 0.88). In addition, subjects with partly controlled or uncontrolled asthma were no more likely to experience moderate or severe treatment-related AEs than subjects with controlled asthma (p = 0.42).ConclusionThe SQ HDM SLIT-tablet is well tolerated, and the safety profile was comparable for subjects with HDM respiratory allergic disease irrespective of asthma status.

| S-EPMC5804837 | biostudies-literature

Definition of a pool of epitopes that recapitulates the T cell reactivity against major house dust mite allergens.

Project description:Allergens from house dust mites (HDM) are a common cause of asthma. Der p and Der f from Dermatophagoides sp. are strong immunogens in humans. Allergen extracts are used to study T helper (Th2) cell responses to HDM, which are implicated in the development and regulation of allergic disease.To define an epitope mixture that recapitulates, and might substitute for, HDM extract in terms of detecting and characterizing Th2 cell responses.Peripheral blood mononuclear cells (PBMC) from 52 HDM allergic and 10 non-allergic individuals were stimulated with HDM extracts and assayed with a set of 178 peptides spanning mite allergens group Der p 1, 2, 23 and Der f group 1 and 2 allergens. A pool of the most dominant T cell epitopes identified in the present study and from published literature was assembled and tested for ex vivo T cell responses. Correlation with HDM-specific IgE titres was examined.Patterns of T cell reactivity to Der p and Der f - derived peptides revealed a large number of epitopes. Clear patterns of immunodominance were apparent, with HDM allergen group 1 and 2 dominant over group 23. Furthermore, within a given antigen, 6-11 epitopes accounted for the vast majority of responses. Based on these results and published data, a comprehensive dust mite pool (DMP) of epitopes was designed and found to allow detection of ex vivo T cell responses. DMP ex vivo reactivity correlated with HDM-specific IgE titres and was similar to that detected with commonly used HDM extracts. Ex vivo DMP stimulation was associated with a predominant Th2 response in allergic donors, and minor reactivity of T cells producing IFNÎ³, IL17 and IL10.A detailed map of Der p and Der f antigens defined a pool of epitopes that can be used to detect ex vivo HDM responses.

| S-EPMC4526447 | biostudies-literature

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