The major allergen Der p 2 is a cholesterol binding protein

Reginald, Kavita; Chew, Fook Tim

doi:10.1038/s41598-018-38313-9

Cited by 26 publications

(23 citation statements)

References 32 publications

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“…But it is speculated that Der p 2 and LPS will strengthen this kind of reaction after forming a complex. However, recent research results show that the natural ligand of Der p 2 is cholesterol, not LPS as previously thought [24].…”

Section: Der Pmentioning

confidence: 78%

Clinical significance of dust mite allergens

Cao

Liu

2020

Mol Biol Rep

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Dust mites are an important cause of allergic diseases worldwide. The traces of Dermatophagoides farinae and Dermatophagoides pteronyssinus can be found all over the world, while Blomia tropicalis are more common allergenic mites in tropical areas. A variety of allergenic components in dust mites have been found, apart from the different positive rates of IgE reactions in dust mite allergic patients, their biological characteristics, effects on the innate immune system, and especially their distribution characteristics in patients are different. Studying the relationship between dust mite allergens and clinical significance will help for diagnosis of patients and formulation of corresponding Allergen Specific Immunotherapy.

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Section: Der Pmentioning

confidence: 78%

Clinical significance of dust mite allergens

Cao

Liu

2020

Mol Biol Rep

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“…The protein sequence of Blo t 2 also contained the ML domain, which is implicated in lipid recognition 27 . Recently, we have demonstrated that cholesterol is the preferred lipid ligand of Der p 2 44 , but further studies are necessary to identify the lipid ligand and its functional role in Blo t 2.…”

Section: Discussionmentioning

confidence: 99%

Blo t 2: Group 2 allergen from the dust mite Blomia tropicalis

Reginald

Pang

Chew

2019

Sci Rep

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Blomia tropicalis has been recognized as a cause of allergic diseases in the tropical and subtropical regions. Here we report the immuno-characterization of its group 2 allergen, Blo t 2. Allergen Blo t 2 was amplified from the cDNA of B. tropicalis using degenerate primers, expressed in Escherichia coli as a recombinant protein and purified to homogeneity. The mature protein of Blo t 2 was 126 amino acids long with 52% sequence identity to Der p 2 and apparent molecular mass of 15 kDa. Circular dichroism spectroscopy showed that Blo t 2 is mainly a beta-sheeted protein. We confirmed the presence of three disulfide bonds in recombinant (r) Blo t 2 protein using electrospray mass spectrometry. Thirty-four percent of dust-mite allergic individuals from the Singapore showed specific IgE binding to rBlo t 2 as tested using immuno dot-blots. IgE-cross reactivity assays showed that Blo t 2 had between 20–50% of unique IgE-epitopes compared to Der p 2. IgE binding of native and recombinant forms of Blo t 2 were highly concordant (r 2 = 0.77, p < 0.0001) to rBlo t 2. Dose-dependent in vitro histamine was observed when rBlo t 2 was incubated with whole blood of Blo t 2 sensitized individuals, demonstrating that it is a functional allergen. Nine naturally occurring isoforms of Blo t 2 were identified in this study, each having between 1–3 amino acid variations compared to the reference clone. Blo t 2 is a clinically relevant allergen of B. tropicalis as it has unique IgE epitopes compared to major group 2 allergens from Dermatophagoides spp .

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“…This would allow to draw conclusion on their contributions in the initiation of the HDM allergic response. The HDM allergens from groups 2,5,7,13,14,21,22,31,35, exhibiting similarities with lipid binding protein and/or showing capacity to interact with lipid cargos, are all susceptible to promote pleiotropic effects on the innate immune system through interactions with TLR2, TLR4 or other receptors as TLR1, TLR6, RAGE, CD14, CD36 (24,28,(58)(59)(60). Whether these proteins play redundant or unique role(s) in the innate immune activation remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Innate Immune Responses to House Dust Mite Allergens: Pitfalls and Limitations

Jacquet

2021

Front.Allergy

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Whereas house dust mite (HDM) allergy results from a dysregulated Th2-biased adaptive immune response, activation of innate immune signaling pathways is a critical prerequisite for the initiation of HDM sensitizations. Such innate sensing is mainly controlled by the airway epithelium and the skin. The resulting release of epithelial-derived proinflammatory cytokines and innate alarmins such as GM-CSF, IL-25, IL-33 and TSLP mediates the activation of ILC2 cells and cDCs to promote Th2-biased inflammation. Significant progress in the elucidation of HDM innate immune activation has been made in the past decade and highlighted key roles of the LPS/TLR4 axis, chitin-dependent pathways together with HDM protease allergens. However, the precise mechanisms by which HDM allergens are sensed by the innate immune system remain largely unknown. Such investigations are made difficult for several reasons. Among these are (1) the natural association of HDM allergens with immunostimulators from the mite exoskeleton as well as from environmental microorganisms/pollutants or endosymbiotic bacteria; (2) the purification of individual HDM allergens from extracts in sufficient amounts and devoid of any microbial and protein impurities; (3) the production of correctly folded recombinant HDM allergens which could display the same biological activity than their natural counterparts; (4) the accessibility to human epithelial samples with cellular heterogeneities and inter-donor variations; (5) the translation of experimental data from mouse models to humans is almost missing. The goal of the present mini-review is to emphasize some important limitations and pitfalls in the elucidation of innate immunostimulatory properties of HDM allergens.

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The major allergen Der p 2 is a cholesterol binding protein

Cited by 26 publications

References 32 publications

Clinical significance of dust mite allergens

Clinical significance of dust mite allergens

Blo t 2: Group 2 allergen from the dust mite Blomia tropicalis

Characterization of Innate Immune Responses to House Dust Mite Allergens: Pitfalls and Limitations

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