Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ACCESS DATA

Json Xml

Publications

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

Similar Datasets

LMAN1 is a receptor for house dust mite allergens.

Project description:Development of therapies with the potential to change the allergic asthmatic disease course will require the discovery of targets that play a central role during the initiation of an allergic response, such as those involved in the process of allergen recognition. We use a receptor glycocapture technique to screen for house dust mite (HDM) receptors and identify LMAN1 as a candidate. We verify the ability of LMAN1 to directly bind HDM allergens and demonstrate that LMAN1 is expressed on the surface of dendritic cells (DCs) and airway epithelial cells (AECs) in vivo. Overexpression of LMAN1 downregulates NF-κB signaling in response to inflammatory cytokines or HDM. HDM promotes binding of LMAN1 to the FcRγ and recruitment of SHP1. Last, peripheral DCs of asthmatic individuals show a significant reduction in the expression of LMAN1 compared with healthy controls. These findings have potential implications for the development of therapeutic interventions for atopic disease.

| S-EPMC10105285 | biostudies-literature

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

Project description:The scabies mite, Sarcoptes scabiei var. hominis, infests human skin, causing allergic reactions and facilitating bacterial infection by Streptococcus sp., with serious consequences such as rheumatic fever and rheumatic heart disease. To identify a possible drug target or vaccine candidate protein, we searched for homologues of the group 3 allergen of house dust mites, which we subsequently identified in a cDNA library. The native protein, designated Sar s 3, was shown to be present in the mite gut and excreted in fecal pellets into mite burrows within the upper epidermis. The substrate specificity of proteolytically active recombinant rSar s 3 was elucidated by screening a bacteriophage library. A preference for substrates containing a RS(G/A) sequence at the P1-P2' positions was revealed. A series of peptides synthesized as internally quenched fluorescent substrates validated the phage display data and high performance liquid chromatography/mass spectrometry analysis of the preferred cleaved substrate and confirmed the predicted cleavage site. Searches of the human proteome using sequence data from the phage display allowed the in silico prediction of putative physiological substrates. Among these were numerous epidermal proteins, with filaggrin being a particularly likely candidate substrate. We showed that recombinant rSar s 3 cleaves human filaggrin in vitro and obtained immunohistological evidence that the filaggrin protein is ingested by the mite. This is the first report elucidating the substrate specificity of Sar s 3 and its potential role in scabies mite biology.

| S-EPMC2797209 | biostudies-literature

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

Project description:Serodominant group 1 allergens of house dust mites (HDMs) are cysteine protease digestive enzymes. By increasing the detection of any allergen by dendritic antigen presenting cells, upregulating inflammatory signalling molecules, and activating cells crucial to the transition from innate to acquired immune responses, the proteolytic activity of these HDM allergens also underlies their behaviour as inhalant allergens. The significance of this property is underlined by the attenuation of allergic responses to HDMs by novel inhibitors in experimental models. The group 1 HDM allergens act as prothrombinases, enabling them to operate the canonical stimulation of protease activated receptors 1 and 4. This leads to the ligation of Toll-like receptor 4, which is an indispensable component in HDM allergy development, and reactive oxidant-regulated gene expression. Intermediate steps involve epidermal growth factor receptor ligation, activation of a disintegrin and metalloproteases, and the opening of pannexons. Elements of this transduction pathway are shared with downstream signalling from biosensors which bind viral RNA, suggesting a mechanistic linkage between allergens and respiratory viruses in disease exacerbations. This review describes recent progress in the characterisation of an arterial route which links innate responses to inhaled allergens to events underpinning the progression of allergy to unrelated allergens.

| S-EPMC6274810 | biostudies-literature

A hypoallergenic peptide mix containing T cell epitopes of the clinically relevant house dust mite allergens.

Project description:BackgroundIn the house dust mite (HDM) Dermatophagoides pteronyssinus, Der p 1, 2, 5, 7, 21, and 23 have been identified as the most important allergens. The aim of this study was to define hypoallergenic peptides derived from the sequences of the six allergens and to use the peptides and the complete allergens to study antibody, T cell, and cytokine responses in sensitized and nonsensitized subjects.MethodsIgE reactivity of HDM-allergic and non-HDM-sensitized individuals to 15 HDM allergens was established using ImmunoCAP ISAC technology. Thirty-three peptides covering the sequences of the six HDM allergens were synthesized. Allergens and peptides were tested for IgE and IgG reactivity by ELISA and ImmunoCAP, respectively. Allergenic activity was determined by basophil activation. CD4+ T cell and cytokine responses were determined in PBMC cultures by CFSE dilution and Luminex technology, respectively.ResultsHouse dust mite allergics showed IgE reactivity only to complete allergens, whereas 31 of the 33 peptides lacked relevant IgE reactivity and allergenic activity. IgG antibodies of HDM-allergic and nonsensitized subjects were directed against peptide epitopes and higher allergen-specific IgG levels were found in HDM allergics. PBMC from HDM-allergics produced higher levels of IL-5 whereas non-HDM-sensitized individuals mounted higher levels of IFN-gamma, IL-17, pro-inflammatory cytokines, and IL-10.ConclusionIgG antibodies in HDM-allergic patients recognize peptide epitopes which are different from the epitopes recognized by IgE. This may explain why naturally occurring allergen-specific IgG antibodies do not protect against IgE-mediated allergic inflammation. A mix of hypoallergenic peptides containing T cell epitopes of the most important HDM allergens was identified.

| S-EPMC7078969 | biostudies-literature

Integrated OMICs Approach for the Group 1 Protease Mite-Allergen of House Dust Mite Dermatophagoides microceras.

Project description:House dust mites (HDMs) are one of the most important allergy-causing agents of asthma. In central Taiwan, the prevalence of sensitization to Dermatophagoides microceras (Der m), a particular mite species of HDMs, is approximately 80% and is related to the IgE crossing reactivity of Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f). Integrated OMICs examination was used to identify and characterize the specific group 1 mite-allergic component (Der m 1). De novo draft genomic assembly and comparative genome analysis predicted that the full-length Der m 1 allergen gene is 321 amino acids in silico. Proteomics verified this result, and its recombinant protein production implicated the cysteine protease and α chain of fibrinogen proteolytic activity. In the sensitized mice, pathophysiological features and increased neutrophils accumulation were evident in the lung tissues and BALF with the combination of Der m 1 and 2 inhalation, respectively. Principal component analysis (PCA) of mice cytokines revealed that the cytokine profiles of the allergen-sensitized mice model with combined Der m 1 and 2 were similar to those with Der m 2 alone but differed from those with Der m 1 alone. Regarding the possible sensitizing roles of Der m 1 in the cells, the fibrinogen cleavage products (FCPs) derived from combined Der m 1 and Der m 2 induced the expression of pro-inflammatory cytokines IL-6 and IL-8 in human bronchial epithelium cells. Der m 1 biologically functions as a cysteine protease and contributes to the α chain of fibrinogen digestion in vitro. The combination of Der m 1 and 2 could induce similar cytokines expression patterns to Der m 2 in mice, and the FCPs derived from Der m 1 has a synergistic effect with Der m 2 to induce the expression of pro-inflammatory cytokines in human bronchial epithelium cells.

| S-EPMC8998267 | biostudies-literature

Effect of air filtration on house dust mite, cat and dog allergens and particulate matter in homes.

Project description:BackgroundIndoor allergens (i.e. from mite, cat and dog) are carried by airborne particulate matter. Thus, removal of particles would reduce allergen exposure. This work aims to assess the performance of air filtration on particulate matter and thus allergen removal in 22 bedrooms.MethodsIndoor air was sampled (with and without air filtration) with a cascade impactor and allergens were measured using enzyme-linked immunosorbent assay (ELISA). Particulate matter (including ultrafine particles) was also monitored.ResultsThe median of allergen reduction was 75.2% for Der f 1 (p < 0.001, n = 20), 65.5% for Der p 1 (p = 0.066, n = 4), 76.6% for Fel d 1 (p < 0.01, n = 21) and 89.3% for Can f 1 (p < 0.01, n = 10). For size fractions, reductions were statistically significant for Der f 1 (all p < 0.001), Can f 1 (PM>10 and PM2.5-10, p < 0.01) and Fel d 1 (PM2.5-10, p < 0.01), but not for Der p 1 (all p > 0.05). PM was reduced in all fractions (p < 0.001). The allergens were found in all particle size fractions, higher mite allergens in the PM>10 and for pet allergens in the PM2.5-10.ConclusionsAir filtration was effective in removing mites, cat and dog allergens and also particulate matter from ambient indoor air, offering a fast and simple solution to mitigate allergen exposome.

| S-EPMC9022093 | biostudies-literature

Der p 5 crystal structure provides insight into the group 5 dust mite allergens.

Project description:Group 5 allergens from house dust mites elicit strong IgE antibody binding in mite-allergic patients. The structure of Der p 5 was determined by x-ray crystallography to better understand the IgE epitopes, to investigate the biologic function in mites, and to compare with the conflicting published Blo t 5 structures, designated 2JMH and 2JRK in the Protein Data Bank. Der p 5 is a three-helical bundle similar to Blo t 5, but the interactions of the helices are more similar to 2JMH than 2JRK. The crystallographic asymmetric unit contains three dimers of Der p 5 that are not exactly alike. Solution scattering techniques were used to assess the multimeric state of Der p 5 in vitro and showed that the predominant state was monomeric, similar to Blo t 5, but larger multimeric species are also present. In the crystal, the formation of the Der p 5 dimer creates a large hydrophobic cavity of approximately 3000 A(3) that could be a ligand-binding site. Many allergens are known to bind hydrophobic ligands, which are thought to stimulate the innate immune system and have adjuvant-like effects on IgE-mediated inflammatory responses.

| S-EPMC2919102 | biostudies-literature

Maternal house dust mite exposure during pregnancy enhances severity of house dust mite-induced asthma in murine offspring.

Project description:BACKGROUND:Atopic status of the mother and maternal exposure to environmental factors are associated with increased asthma risk. Moreover, animal models demonstrate that exposure to allergens in strongly sensitized mothers influences offspring asthma development, suggesting that in utero exposures can influence offspring asthma. However, it is unclear whether maternal exposure to common human allergens such as house dust mite (HDM), in the absence of additional adjuvants, influences offspring asthma development. OBJECTIVE:We sought to determine whether maternal HDM exposure influences asthma development in offspring. METHODS:Pregnant female mice were exposed to PBS or HDM during pregnancy. Using offspring of PBS- or HDM-exposed mothers, the magnitude of HDM or Aspergillus fumigatus (AF) extract-induced airway hyperresponsiveness (AHR), airway inflammation, immunoglobulin production, TH2-associated cytokine synthesis, and pulmonary dendritic cell activity was assessed. RESULTS:Compared with offspring of PBS-exposed mothers, offspring of HDM-exposed mothers demonstrate increased AHR, airway inflammation, TH2 cytokine production, and immunoglobulin levels and a modest decrease in the phagocytic capacity of pulmonary macrophage populations following HDM exposure. Increased sensitivity to AF-induced airway disease was not observed. Offspring of HDM-exposed B-cell-deficient mothers also demonstrated increased HDM-induced AHR, suggesting that transfer of maternal immunoglobulins is not required. CONCLUSIONS:Our data demonstrate that maternal exposure to HDM during pregnancy increases asthma sensitivity in offspring in an HDM-specific manner, suggesting that vertical transmission of maternal immune responses may be involved. These findings have important implications for regulation of asthma risk, and suggest that exposure to HDM in the developed world may have underappreciated influences on the overall prevalence of allergic asthma.

| S-EPMC5550362 | biostudies-literature

Group 10 allergens (tropomyosins) from house-dust mites may cause covariation of sensitization to allergens from other invertebrates.

Project description:Group 10 allergens (tropomyosins) have been assumed to be a major cause of cross-reactivity between house-dust mites (HDMs) and other invertebrates. Despite all of the published data regarding the epidemiology, percent IgE binding and level of sensitization in the population, the role of tropomyosin as a cross-reactive allergen in patients with multiple allergy syndrome still remains to be elucidated. Homology between amino acid sequences reported in allergen databases of selected invertebrate tropomyosins was determined with Der f 10 as the reference allergen. The 66.9 and 54.4% identities were found with selected crustacean and insect species, respectively, whereas only 20.4% identity was seen with mollusks. A similar analysis was performed using reported B-cell IgE-binding epitopes from Met e1 (shrimp allergen) and Bla g7 (cockroach allergen) with other invertebrate tropomyosins. The percent identity in linear sequences was higher than 35% in mites, crustaceans, and cockroaches. The polar and hydrophobic regions in these groups were highly conserved. These findings suggest that tropomyosin may be a major cause of covariation of sensitization between HDMs, crustaceans, and some species of insects and mollusks.

| S-EPMC3548612 | biostudies-literature

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

Project description:Diverse evidence from epidemiologic surveys and investigations into the molecular basis of allergenicity have revealed that a small cadre of "initiator" allergens promote the development of allergic diseases, such as asthma, allergic rhinitis, and atopic dermatitis. Pre-eminent among these initiators are the group 1 allergens from house dust mites (HDM). In mites, group 1 allergens function as cysteine peptidase digestive enzymes to which humans are exposed by inhalation of HDM fecal pellets. Their protease nature confers the ability to activate high gain signaling mechanisms which promote innate immune responses, leading to the persistence of allergic sensitization. An important feature of this process is that the initiator drives responses both to itself and to unrelated allergens lacking these properties through a process of collateral priming. The clinical significance of group 1 HDM allergens in disease, their serodominance as allergens, and their IgE-independent bioactivities in innate immunity make these allergens interesting therapeutic targets in the design of new small-molecule interventions in allergic disease. The attraction of this new approach is that it offers a powerful, root-cause-level intervention from which beneficial effects can be anticipated by interference in a wide range of effector pathways associated with these complex diseases. This review addresses the general background to HDM allergens and the validation of group 1 as putative targets. We then discuss structure-based drug design of the first-in-class representatives of allergen delivery inhibitors aimed at neutralizing the proteolytic effects of HDM group 1 allergens, which are essential to the development and maintenance of allergic diseases.

| S-EPMC6064784 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data