Hazelnut (Corylus avellana) vicilin Cor a 11: molecular characterization of a glycoprotein and its allergenic activity

Abstract

In Europe, hazelnuts (Corylus avellana) are a frequent cause of food allergies. Several important hazelnut allergens have been previously identified and characterized. Specific N-glycans are known to induce strong IgE responses of uncertain clinical relevance, but so far the allergenic potential of glycoproteins from hazelnut has not been investigated. The aim of the study was the molecular characterization of the glycosylated vicilin Cor a 11 from hazelnut and the analysis of its allergenic activity. Although MALDI-TOF (matrix-assisted laser-desorption ionization-time-of-flight) MS showed that one of two potential glycosylation sites of Cor a 11 was glycosylated, CD spectroscopy indicated that recombinant and natural Cor a 11 share similar secondary structures. Thus to analyse the impact of the glycan residues of Cor a 11 on IgE binding, the allergenic activity of natural glycosylated Cor a 11 and recombinant Cor a 11 was compared. In addition, the IgE sensitization pattern to recombinant Cor a 11, Cor a 1, Cor a 2 and Cor a 8 of 65 hazelnut allergic patients was determined in vitro. The prevalence of IgE reactivity to hazelnut vicilin Cor a 11 was below 50%. Basophil histamine-release assays were used to determine the allergenic activity of both natural and recombinant Cor a 11 in comparison with Cor a 1, a birch (Betula verrucosa) pollen-related major hazelnut allergen. Both forms of Cor a 11 induced mediator release from basophils to a similar extent, indicating that the hazelnut allergic patients had cross-linking IgE antibodies binding to the protein backbone and not to carbohydrate structures. In comparison to Cor a 1, a 10000-fold higher concentration of Cor a 11 was required to induce similar basophil mediator release. In conclusion, the hazelnut vicilin Cor a 11 is a minor allergen both in regard to prevalence and allergenic potency, whereas its glycan does not contribute to its allergenic activity.

The Role of Protein Glycosylation in Allergy

“…Similar results were found for the glycoproteins orange germin-like protein (Cit s 1) and latex Hev b 2 [95, 96]. Also, the carbohydrate of vicilin (mainly MMX) was found not to contribute to eliciting symptoms [41]. Because of this clinical insignificance, CCD epitopes and in many cases also profilin can be seen as ‘mimickers of allergy’ [4].…”

“…Tree pollens [30] and tree pollen allergens [39] tend to bear terminal non-reducing GlcNAc residues, a feature which may reduce IgE binding (see paragraph on specificity of IgG). Olive pollen Ole e 1, hazelnut Cor a 11 and peanut Ara h 1 differ by essentially lacking the core fucosyl residue [38, 40, 41]. In contrast, Cyn d 24 and other glycoproteins from Bermuda grass pollen carry non-xylosylated glycans, mainly MMF 3 (fig.…”

Scientific Opinion on the evaluation of allergenic foods and food ingredients for labelling purposes

“…Sensitisation to Cor a 9 can appear in very young infants prior to tree pollen sensitisation and independently from sensitisation to its homologues in legumes such as soy or peanut . IgE binding to Cor a 11 was found in 31 of 65 adult patients with hazelnut OAS (Lauer et al, 2004). Sensitisation to Cor a 11 was seen in 12 of 32 of children with systemic reactions to hazelnut and only in one out of eight adult patients (Verweij et al, 2012).…”

Functional Interaction of Common Allergens and a C-type Lectin Receptor, Dendritic Cell-specific ICAM3-grabbing Non-integrin (DC-SIGN), on Human Dendritic Cells

“…Both BG60 and Cor a11 are known to contain fucosylated glycan (14,16), a preferred ligand of DC-SIGN. In addition to DC-SIGN, a number of CLRs are known to be expressed on circulating DCs, except for L-SIGN, which is a CLR primarily expressed in lymphoid endothelium.…”

“…In contrast, allergens of Bermuda grass pollens, such as BG60, carry MMF-type structure without xylose linkage to the terminal mannose (14). Some allergens, such as peanut Ara h 1, lack the core fucosyl residue (15), whereas a hazelnut allergen, Cor a11, carries a mixed type of glycan structures, MMX and MMXF (16).…”