Identification of the cysteine protease Amb a 11 as a novel major allergen from short ragweed

Bouley, J.; Groeme, Rachel; Mignon, Maxime Le; Jain, K.; Chabre, Henri; Floch, Véronique Bordas-Le; Couret, Marie-Noëlle; Bussières, Laetitia; Lautrette, Aurélie; Naveau, Marie; Baron‐Bodo, Véronique; Lombardi, Vincent; Mascarell, Laurent; Batard, Thierry; Nony, Emmanuel; Moingeon, Philippe

doi:10.1016/j.jaci.2015.03.001

Cited by 51 publications

(56 citation statements)

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“…Our previously published data established a 66% prevalence of IgE reactivity against the natural Amb a 11 allergen in allergic patients (9). Although not shown, nAmb a 11 from ragweed pollen extract, pro-rAmb a 11, and rAmb a 11 reacted similarly with serum IgEs from ragweed pollen-allergic patients as well as sheep polyclonal and murine monoclonal antibodies, clearly indicating that IgE and IgG epitopes are preserved in the recombinant molecules.…”

Section: Discussionmentioning

confidence: 68%

“…Although as of today 10 short ragweed pollen allergens have been officially registered by International Union of Immunological Societies (6), we recently reported the identification of seven novel candidate allergens following an extensive characterization of the short ragweed pollen transcriptome and proteome (26). Among those molecules, only two are considered as major allergens, namely, the pectate lyase Amb a 1 and the cysteine protease Amb a 11 (9), thought to contribute jointly to most of the ragweed pollen allergenicity. Whereas Amb a 1 has been extensively characterized (27), the structure, activity, and allergenicity of Amb a 11 are not yet fully documented.…”

Section: Discussionmentioning

confidence: 99%

“…As of today, 10 short ragweed pollen allergens have been registered by the International Union of Immunological Societies (6). Among them, two are considered as major allergens, including the pectate lyase Amb a 1 and the cysteine protease Amb a 11, which are recognized by serum IgE of 90% (7,8) and 66% (9), respectively, of ragweed pollen-allergic patients. We recently identified natural Amb a 11 as a 28-kDa glycosylated protein displaying amino acid sequence identities with other allergens belonging to the C1A cysteine protease family, such as Der p 1 and Der f 1 (from house dust mite Dermatophagoides sp.…”

mentioning

confidence: 99%

“…We recently identified natural Amb a 11 as a 28-kDa glycosylated protein displaying amino acid sequence identities with other allergens belonging to the C1A cysteine protease family, such as Der p 1 and Der f 1 (from house dust mite Dermatophagoides sp. ; 24.4 and 26.0% identity, respectively), the actinidin Act d 1 (from Actinidia deliciosa; 37% identity), and papain (from Carica papaya; 34.6% identity) molecules (9). The Amb a 11 gene (GenBank TM accession number KF528831) codes for a precursor molecule of 364 residues encompassing both N-and C-terminal propeptides and preceded by a signal sequence of 22 amino acids (UniProt accession V5LU01_AMBAR) (9).…”

mentioning

confidence: 99%

“…; 24.4 and 26.0% identity, respectively), the actinidin Act d 1 (from Actinidia deliciosa; 37% identity), and papain (from Carica papaya; 34.6% identity) molecules (9). The Amb a 11 gene (GenBank TM accession number KF528831) codes for a precursor molecule of 364 residues encompassing both N-and C-terminal propeptides and preceded by a signal sequence of 22 amino acids (UniProt accession V5LU01_AMBAR) (9).…”

mentioning

confidence: 99%

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Structural and Functional Characterization of the Major Allergen Amb a 11 from Short Ragweed Pollen

Groeme¹,

Airouche²,

Kopečný³

et al. 2016

Journal of Biological Chemistry

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Allergy to the short ragweed (Ambrosia artemisiifolia) pollen is a major health problem. The ragweed allergen repertoire has been recently expanded with the identification of Amb a 11, a new major allergen belonging to the cysteine protease family. To better characterize Amb a 11, a recombinant proform of the molecule with a preserved active site was produced in Escherichia coli, refolded, and processed in vitro into a mature enzyme. The enzymatic activity is revealed by maturation following an autocatalytic processing resulting in the cleavage of both N-and C-terminal propeptides. The 2.05-Å resolution crystal structure of pro-Amb a 11 shows an overall typical C1A cysteine protease fold with a network of molecular interactions between the N-terminal propeptide and the catalytic triad of the enzyme. The allergenicity of Amb a 11 was confirmed in a murine sensitization model, resulting in airway inflammation, production of serum IgEs, and induction of Th2 immune responses. Of note, inflammatory responses were higher with the mature form, demonstrating that the cysteine protease activity critically contributes to the allergenicity of the molecule. Collectively, our results clearly demonstrate that Amb a 11 is a bona fide cysteine protease exhibiting a strong allergenicity. As such, it should be considered as an important molecule for diagnosis and immunotherapy of ragweed pollen allergy.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Structural and Functional Characterization of the Major Allergen Amb a 11 from Short Ragweed Pollen

Groeme¹,

Airouche²,

Kopečný³

et al. 2016

Journal of Biological Chemistry

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Acaciain peptidase: The first South American pollen peptidase potentially involved in respiratory allergy

Barcia

Coelho

Barberis

et al. 2019

Biotech and App Biochem

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Acacia caven (Mol.) Molina pollen causes pollinosis in South America. The aim of this work was to isolate, purify, and characterize the proteolytic enzymes of A. caven pollen, and study their influence on allergy. A series of chromatographic steps were applied to purify the proteolytic extract of A. caven pollen. The purified fraction was partially characterized, and then it was assayed on airway bioactive peptides (substance P, vasoactive intestinal peptide, and bradykinin), and peptide degradation was visualized by direct protein sequencing. The cellular detachment of an airway‐derived epithelial cell line (A‐549) was measured by methylene blue binding assay. The degradation of proteins from intercellular junctions (occludin, claudin, and E‐cadherin) was visualized by Western blot. A 75‐kDa peptidase, named acaciain peptidase, was purified and classified as a serine peptidase. Acaciain peptidase degraded bioactive peptides involved in the maintenance and recovery of the bronchomotor tone; it caused cellular detachment of A‐549 cell line, and degradation of intercellular junction proteins. Acaciain peptidase can alter the integrity of the epithelium barrier, causing cell permeability, increasing the allergic sensitization and exacerbating the overall bronchoconstrictive effect detected in asthmatic lungs. This novel serine peptidase constitutes a relevant therapeutic target in the treatment of allergic disorders.

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Complex IgE sensitization patterns in ragweed allergic patients: Implications for diagnosis and specific immunotherapy

Buzan

Zbîrcea

Gattinger

et al. 2022

Clinical & Translational All

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Background Ragweed (Ambrosia artemisiifolia) is one of the most important allergen sources, worldwide, causing severe respiratory allergic reactions in late summer and fall, in sensitized patients. Amb a 1 has been considered as the most important allergen in ragweed but 12 ragweed pollen allergens are known. The aim of our study was to investigate IgE reactivity profiles of ragweed allergic patients and to associate them with clinical symptoms. Methods IgE sensitization profiles from clinically well‐characterized ragweed allergic patients (n = 150) were analyzed using immunoblotted ragweed pollen extract. Immunoblot inhibition experiments were performed with two Amb a 1 isoforms and CCD markers and basophil activation experiments were performed with IgE serum before and after depletion of Amb a 1‐specific IgE. Results By IgE‐immunoblotting 19 different IgE reactivity patterns with and without Amb a 1‐sensitization were found. The majority of patients (>95%) suffered from rhino‐conjunctivitis, around 60% reported asthma‐like symptoms and about 25% had skin reactions. Patients with complex IgE sensitization profiles tended to have more clinical symptoms. Serum with and without Amb a 1‐specific IgE induced basophil activation. Conclusions Ragweed pollen allergic patients exhibit complex IgE reactivity profiles to ragweed allergens including Amb a 1 isoforms and cross‐reactive carbohydrates indicating the importance of Amb a 1 isoforms and additional allergens for diagnosis and allergen‐specific immunotherapy of ragweed allergy.

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Identification of the cysteine protease Amb a 11 as a novel major allergen from short ragweed

Abstract: We identified the cysteine protease Amb a 11 as a new major allergen from ragweed pollen. Given the similar physicochemical properties shared by the 2 major allergens, we hypothesize that part of the allergenic activity previously ascribed to Amb a 1 is rather borne by Amb a 11.

Cited by 51 publications

References 36 publications

Structural and Functional Characterization of the Major Allergen Amb a 11 from Short Ragweed Pollen

Structural and Functional Characterization of the Major Allergen Amb a 11 from Short Ragweed Pollen

Acaciain peptidase: The first South American pollen peptidase potentially involved in respiratory allergy

Complex IgE sensitization patterns in ragweed allergic patients: Implications for diagnosis and specific immunotherapy

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