Mutational Analysis of Amino Acid Positions Crucial for IgE-Binding Epitopes of the Major Apple &lt;i&gt;(Malus domestica)&lt;/i&gt; Allergen, Mal d 1

Ma, Yan; Gadermaier, Gabriele; Bohle, Barbara; Bolhaar, Suzanne; Knulst, André C.; Marković-Housley, Z.; Breiteneder, Heimo; Briza, Peter; Hoffmann‐Sommergruber, Karin; Ferreira, Fátima

doi:10.1159/000089756

Cited by 69 publications

(69 citation statements)

References 91 publications

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“…Moreover, site-directed mutagenesis has been used successively to produce low IgE-reactive recombinant forms of the popular allergens such as major apple allergen Mal d 1 and birch pollen allergen Bet v 1. [24][25][26] These results have shown that replacement of only a few key amino acids within an allergen molecule can significantly reduce the human IgE reactivity of these allergenic proteins. Modified recombinant allergens exhibiting reduced allergenicity seem to decrease the risk of symptoms and to be useful for immunotherapy.…”

Section: Discussionmentioning

confidence: 95%

Immunological Characterization and Mutational Analysis of the Recombinant Protein BWp16, a Major Allergen in Buckwheat

Satoh

Koyano

Takagi

et al. 2008

Biological & Pharmaceutical Bulletin

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Buckwheat allergy is one of the most critical diseases manifested by severe and dangerous symptoms in Japan and other countries. We previously isolated the cDNA encoding protein BWp16, a member of the 2S albumin family with a conserved motif of 8 cysteine (Cys) residues. Comparison of the deduced amino acid sequences of BWp16 and related proteins in the 2S albumin family showed similarities between BWp16 and BW 8-kDa from buckwheat, Ara h 6 from peanuts and Ric c 1 from castor bean. Purified recombinant BWp16 (rBWp16) expressed in Escherichia coli was recognized by Ͼ80% of sera from patients with positive for IgE binding to buckwheat. Mutational analysis of rBWp16 revealed that 7 out of 10 mutants in the Cys residues showed weaker IgE binding to patient's serum than wild-type rBWp16 (rBWp16 WT). Mutations of Cys65 and Cys66 in rBWp16 decreased the pepsin digestibility of the protein, and an ELISA inhibition assay revealed a weaker inhibitory effect of rBWp16 C65S than that of rBWp16 WT. These results suggest that the Cys residues, especially Cys65, are involved in the allergenicity of rBWp16. Our findings provide new evidence for the role of Cys residues in 2S albumin family proteins and open the door to the production of hypoallergens and application to safe diagnostic methods and allergen-specific immunotherapy of buckwheat allergy.

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Section: Discussionmentioning

confidence: 95%

Immunological Characterization and Mutational Analysis of the Recombinant Protein BWp16, a Major Allergen in Buckwheat

Satoh

Koyano

Takagi

et al. 2008

Biological & Pharmaceutical Bulletin

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“…Site-specific mutagenesis can be a valid tool to identify the essential role of single amino acid substitution in immunological response [9,17]. With this method, the region 38-55 of Par j 2 has been shown to be the most powerful for eliciting allergenic reaction in the serum of atopic individuals.…”

Section: Discussionmentioning

confidence: 99%

Amino Acid Substitution in Par j 2 Recombinant Allergen and Its Effect on IgE Binding Capacity

Nuzzo

Pizzo

Albeggiani

et al. 2009

Scholarly Research Exchange

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Therapeutic attempts to cure allergic diseases reduce symptoms without circumventing the onset of the allergic reaction. Specific immunotherapy (SIT), is the most commonly used treatment. Nevertheless, SIT may account for various adverse events. Therefore, different therapies have been developed in order to treat and prevent allergic reactions. Among these therapies, there is an increased interest in studying recombinant peptides mutated in the IgE binding site. Several studies have shown two major allergens of Parietaria judaica (Pj) named Par j 1 and Par j 2, which have been cloned and characterized by us. In our study we have fragmented the Par j 2 protein in order to determine the major epitopes recognized by human IgE and we used site-directed mutagenesis to identify potential amino acid residues involved in IgE binding. The IgE binding activity of the recombinant peptides was tested and the results showed that site-specific mutagenesis at positions K41, T42, T43, and C52 caused a loss of IgE binding. The goal of this work is to synthesize molecules which can induce a protective immune response against Pj. These molecules will be used in immunotherapy in order to create new vaccines for the treatment of Parietaria pollen allergy.

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“…The epitope must be classified as discontinuous. However, residues 42-52 (including the alleged "P-loop like" region 46-51 of the Bet v 1 sequence) constitute 80% of the contact surface (Ma et al, 2006).…”

Section: Prediction Of the Ige Binding Sites To The Amino Acid Residumentioning

confidence: 99%

Investigation of Mal d 1 Allelic Variants and Phylogenetic Diversity in Contemporary and Historical Polish Apple Cultivars

Bokszczanin¹,

Przybyla²,

Krezdorn³

et al. 2015

JAS

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Allergy is considered as the most common health problem of XXI century. Apple allergenicity is of great importance and at present the only therapy for food allergy is avoidance. Fruits are important components of a healthy diet, and therefore complete avoidance of apple and related fruits like pear, peach, and cherry can have a significant negative impact since deprives the patient's diet from important sources of vitamins, minerals and fibers. In order to provide a contribution towards a better understanding of the genetics of the family of Mal d 1 gene, the major apple allergen, and to establish the basis for further research on allelic diversity among cultivars in relation to variation in allergenicity we evaluated Mal d 1 gene variability in contemporary and historical Polish apple cultivars (Malus × domestica Borkh.). We identified new Mal d 1 alleles and further assessed phylogenetic distance between Mal d 1 variants and antigens derived from other food sources. We also predicted possible cross-reactions between allergens originated from Malus x domestica and other plant taxa as well as showed potential binding sites of apple allergens to the antibody. Thanks to multiple sequence alignment of the amino acid sequences limited to residues which serve as interaction partners for the antibody we were able to more precisely establish phylogenetic distance between analyzed antigens in regards to the antigen epitope residues.

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Mutational Analysis of Amino Acid Positions Crucial for IgE-Binding Epitopes of the Major Apple <i>(Malus domestica)</i> Allergen, Mal d 1

Cited by 69 publications

References 91 publications

Immunological Characterization and Mutational Analysis of the Recombinant Protein BWp16, a Major Allergen in Buckwheat

Immunological Characterization and Mutational Analysis of the Recombinant Protein BWp16, a Major Allergen in Buckwheat

Amino Acid Substitution in Par j 2 Recombinant Allergen and Its Effect on IgE Binding Capacity

Investigation of Mal d 1 Allelic Variants and Phylogenetic Diversity in Contemporary and Historical Polish Apple Cultivars

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