Peanuts are the seeds of an annual legume, which grows close to the ground and produces its fruit below the soil surface. This is in contrast to tree nuts like Walnuts and Almonds. Peanut is a member of the Fabaceae or legume family, whereas tree nuts are not.
Multiple Peanut varieties are grown, with more than 40% of the American Peanut crop consumed as Peanut butter (1). Runners have become the dominant Peanut type grown in the U.S. due to the spectacular increase in yield that they allow; they are a very important source of Peanut butter. Virginias have the largest kernels and account for most of the Peanuts roasted and sold in their shells. Spanish peanuts have smaller kernels covered with a reddish-brown skin. Valencias are small, very sweet Peanuts usually roasted and sold in the shell, or boiled, but seldom used in processed foods.
The difference in the methods of preparing Peanut as practiced in China compared with that widely used in the United States and Western countries may help explain the difference in prevalence of Peanut allergy observed (28). Roasting of Peanut uses higher temperatures (150-170 °C) than boiling (100 °C) or frying (120 °C), and roasting has been shown to increase the allergenic property of Peanut proteins (2).
However, part of the difference in allergenicity may not be as a result of the heat-treatment per se but as a result of other factors. Some authors suggest that the decrease in allergenicity of boiled Peanuts results mainly from a transfer of low-molecular-weight allergens into the water during cooking (3). Allergen content may vary depending on the Peanut variety and may explain the differences in the prevalence of sensitisation between different population studies (4).
The major Peanut allergens are homologous to the seed storage proteins of the conglutin, vicilin, and glycinin families (5).
Peanut proteins were originally classified as albumins (water-soluble) or globulins (saline-soluble); the globulins were in turn subdivided into arachin and conarachin fractions (the major storage proteins). Components of the albumin fraction of Peanuts are agglutinins, lectin-reactive glycoproteins, protease inhibitors, alpha-amylase inhibitors and phospholipases (6).
Peanut contains, among other, storage and non-storage proteins. The allergens, Ara h 1, Ara h 2, Ara h 3, Ara h 4, Ara h 6, Ara h 7 are seed storage proteins. The major Peanut allergen, Ara h 1, is a heat stable 7S vicilin-like globulin, Ara h 2 is a conglutin (functioning as a trypsin inhibitor), and Ara h 3 is a glycinin. A 59% sequence identity exists between Ara h 2 and Ara h 6, and 35% between Ara h 2 and Ara h 7 (7).
Peanut contains up to 32 different proteins, of which at least 18 have been identified as being capable of binding allergen-specific IgE antibodies (8-9). Varieties of Peanuts from different parts of the world contain similar proteins, including Ara h 1 and Ara h 2, and the IgE-binding properties have also been reported to be similar to a great extent (10).
Allergens characterised to date include:
Ara h 3 and Ara h 4 are regarded as isoforms of each other, i.e., Ara h 4 and Ara h 3 are considered to be the same allergen (13,20).
Ara h 1 comprises 12% to 16% of the total protein in Peanut in population studies, sensitisation to Ara h 1 was found in 95% of Peanut-allergic patients from North America (6,21-23), but in fewer Peanut-allergic patients of 3 European populations, varying from 35% to 70% (1,15,24-25). These differences were not reported for Ara h 2, even though Peanuts from different varieties and from different parts of the world contain similar proteins and the IgE binding properties are similar (10). Unidentified Peanut proteins with molecular weights somewhat lower than 15 kDa may be important allergens as well (26). Ara h 3 is recognised by serum IgE from 45% - 50% of patients with Peanut sensitivity (27). Ara h 5 shows up to 80% amino acid sequence identity with the panallergen profilin, but is present only in low amounts in Peanut extracts. 13% to 16% of Peanut-allergic individuals are sensitised to Peanut profilin (28). Nonetheless, a number of peanut allergens are involved in the sensitisation process.
Sensitisation to Peanut occurs with a high degree of heterogeneity to a number of Peanut allergens. Mono-sensitisation to a single Peanut allergen is relatively rare (29). Although sensitisation to Ara h 1 and Ara h 2 occurs in the great majority of Peanut-allergic individuals, the wide range of allergens present in whole Peanut protein extract appears to be most appropriate to consider when testing for Peanut allergy (23).
For example, in a British study, evaluating sera of 40 Peanut-allergic individuals, of 18 allergens identified, 8 were bound by >50% of patients. The study concluded that promiscuity of IgE binding appears more important than the recognition of individual proteins (30).
Furthermore, some Peanut-allergic subjects fail to bind to either Ara h 1 or 2 suggesting that whole Peanut, rather than Ara h 1 or 2, or the use of individual Peanut allergens would be more appropriate for measuring allergen-specific-IgE responses. This also illustrates that the relative contribution of all Peanut allergens needs to be investigated (23).
In a recent Dutch study examining the IgE reactivity to major Peanut allergens in 20 Peanut-allergic children at two subsequent time-points, before DBPCFC, all 20 Peanut-allergic children were shown to have IgE antibodies to Ara h 2, 16 to Ara h 6, and 10 to both Ara h 1 and Ara h 3. After 20 months, Peanut-specific IgE levels and the individual recognition of major allergens were comparable with the levels and recognition before challenge. Skin reactivity was detected to Ara h 2 and Ara h 6 in most children, whereas for Ara h 1 and Ara h 3 in approximately 50% of the children. No parameters could be related to the severity of Peanut allergy (31).
The availability of recombinant Peanut allergens has resulted in a greater ability to assess the sensitisation and clinical profiles of individual Peanut allergens in different population groups. This is illustrated by a number of studies.
In an evaluation of recombinant allergens, Ara h 1, Ara h 2, and Ara h 3, using sera of 77 American Peanut-allergic patients, seven different patterns of sensitisation were identified. The majority of patients (97%) had IgE antibodies to at least one of the recombinant allergens (Ara h 1,
Ara h 2, and Ara h 3), and 77%, 75% and 77% recognized rAra h1, rAra h 2 and rAra h 3 respectively. High epitope diversity was found in patients with a history of more severe allergic reactions (32).
A European study evaluating sera from 40 patients for sensitisation to six recombinant Peanut allergens, showed 14 individual recognition patterns. Of the sera, Ara h 1 was recognized by 65%, Ara h 2 by 85%, Ara h 4 by 53%, Ara h 5 by 13%, Ara h 6 by 38% and Ara h 7 by 43% (14).
Similarly, a French and American study aimed at evaluating the diagnostic value of the 3 major recombinant Peanut allergens utilizing skin test and serum IgE antibody determination in 30 Peanut-allergic patients. All patients with Peanut allergy demonstrated skin reactivity to rAra h 2; 40% reacted with rAra h 1 and 27% with rAra h 3. Monosensitisation to rAra h 2 was observed in 53% of patients. Levels of allergen-specific IgE did not correlate with the disease severity. However, patients with monosensitisation to rAra h 2 had a significantly lower severity score than polysensitised subjects and a lower level of allergen-specific IgE against Peanut extract and rAra h 2. Cosensitisation to rAra h 2 and rAra h 1 and/or rAra h 3 appeared to be predictive of more severe reactions (33).
A recent Dutch study investigated whether a sensitisation to individual allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6 could be correlated with clinical severity. Purified Peanut allergens were utilized for skin test and IgE antibody evaluation in 30 patients. The majority of patients were found to have allergen-specific IgE to Ara h 2 (25/30, 83%) and Ara h 6 (26/30, 87%). Sixteen patients (53%) were sensitised to Ara h 1 and 15 patients (50%) to Ara h 3. All patients with skin reactivity for Ara h 1 and/or Ara h 3 were also sensitised to Ara h 2 and/or Ara h 6. Patients with severe symptoms had a higher skin response to Ara h 2 and Ara h 6 at low concentrations (0.1 mug/ml) and to Ara h 1 and Ara h 3 at higher concentrations (100 mug/ml) compared with patients with mild symptoms. Patients with more severe symptoms also recognized a greater number of allergens and showed a higher cumulative skin response than with patients with mild symptoms. Ara h 2 and Ara h 6 appeared to be more potent than Ara h 1 and Ara h 3. Both skin reactivity to low concentrations of Ara h 2 and Ara h 6 and to higher concentrations of Ara h 1 and Ara h 3 were shown to be indicative of severe symptoms (34).
Recombinant Peanut allergens have been evaluated for their ability to predict the outcome of tolerance in Peanut-allergic individuals. An American study was performed using sera from 15 patients with symptomatic Peanut allergy and 16 patients who were sensitized but tolerant (of which 10 of these 16 patients had ”outgrown” their allergy) investigated 8 peptides representing the immunodominant sequential epitopes on Ara h 1, 2, and 3. It was found that regardless of their Peanut-specific IgE levels, most patients with symptomatic Peanut allergy showed IgE binding to the 3 immunodominant epitopes on Ara h 2. In contrast, each of these epitopes was recognized by < 10% of the tolerant patients. Tolerant patients did not recognize 2 immunodominant epitopes on Ara h 1. At least 93% of symptomatic, but only 12.5% of tolerant patients, recognized 1 of these “predictive” epitopes on Ara h 1 or Ara h 2. With up to 50% of patients with Peanut-specific IgE levels below suggested diagnostic decision levels still being clinically reactive, oral food challenges could be avoided in approximately 90% of these patients through the determination of peptide-specific IgE. This study analyzed only selected allergen epitopes rather than whole proteins (35).
Recombinant non-glycosylated protein produced in an E. coli strain carrying a cloned cDNA encoding Arachis hypogaea allergen Ara h 1
Common name: Conarachin, Vicilin
Biological function: 7S Vicilin-like globulin
Mw: 65 kDa
Ara h 1 is a vicilin, a member of the 7S vicilin-like globulin family (11,14,25,33-34, 36-40,41-54). It is also known as Conarachin. Ara h 1 is a 65 kDa protein that comprises 12% to 16% of the total protein in Peanut extracts (25) and causes sensitization from 35% to 95% of patients with Peanut allergy, depending on the population group studied (14,21,23-24,26-27,33,44,55). Ara h 1 has been reported to form a stable trimeric protein (21) but upon purification of native Ara h 1 from Peanuts using only size exclusion chromatography, the allergen appeared to exist in an oligomeric structure rather than as a trimeric structure (49).
Seed storage proteins commonly comprise various groups of multiple isoforms encoded by different gene families. Arachin (11S globulin), conarachin (7S globulin) and conglutin (albumin) are the three major storage proteins in Peanut.
Ara h 1 has high sequence similarity with other plant vicilins (36).
Studies have demonstrated the changes that may occur to Ara h 1 during heat processing that may play a role in the allergenicity of Ara h 1 (52, 56). Oven-roasted Peanut (177 °C for 5-30 min) resulted in a level of Ara h 1 that were up to 22-fold higher than in raw Peanut (820 vs. 37 mug/ml) (34).
In vitro gastric digestion was reported to result in rapid degradation of Ara h 1 into small fragments. However, gastric digestion did not affect the ability of Ara h 1 to stimulate cellular proliferation and histamine release of basophils from Peanut allergic individuals was induced to the same extent by native Ara h 1 and its digestion products. Therefore gastro-duodenal digestion fragments of Ara h 1 retain T cell stimulatory and IgE-binding and cross-linking properties of the intact protein (57). This finding is supported by an earlier study that indicated that although at least twenty-three different linear IgE-binding epitopes had been located throughout the length of the Ara h 1 protein that some epitopes are major binding sites resulting in significant Peanut-antibody binding even if Ara h 1 were cleaved into peptides. The cleaving-off of an N-terminal peptide from Ara h 1, which contains three allergenic epitopes of which two are major, found that Peanut-specific IgE-antigen binding occurred as a result of the epitopes that are contained in the cleaved-off peptide, implying that the peptide, or part of it, is still present in Peanuts that are consumed (11).
Other factors may play a role in heat or digestion of Ara h 1. For instance, Ara h 1 has been shown to resist proteolysis when in a trimeric configuration, a property that may contribute to its allergenicity (47).
Ara h 1 and Ara h 2 were also reported to bind higher levels of IgE and were more resistant to heat and digestion by gastrointestinal enzymes once they had undergone the Maillard reaction (58). Roasted Peanut from two different sources bound IgE from patients with Peanut allergy at approximately 90-fold higher levels than the raw Peanut from the same Peanut cultivars (57).
Between 35%-95% of Peanut-allergic individuals are sensitized to Ara h 1 (14,21,23-24,26-27,33,36-41,44). The prevalence of sensitization to a specific Peanut allergen varies between population groups (33).
Sensitization and clinical effects of maternal peanut intake may occur soon after birth in breast-fed infants. Both major Peanut allergens Ara h 1 and Ara h 2 were detected (40).
Peanut is a very potent allergen and exposure to this allergen through saliva via kissing and utensils may cause local and systemic allergic reactions and saliva has been shown to contain up to 1110 mg/ml Ara h 1 (41). Another study concluded that patients with Peanut allergy require counseling regarding risks of kissing or sharing utensils, even if partners have brushed teeth or chewed gum (40).
Recombinant allergens may also play a role in the evaluation of cross-reactivity between plant families. Ara h 1 is a vicilin, a member of the 7S vicilin-like globulin family, and therefore cross-reactivity between Ara h 1 and other vicilins is likely (39). For example, the vicilin allergen Ara h 1 accounts for the IgE-binding cross-reactivity commonly observed between the vicilin allergens from edible legume seeds such as Lentil (Len c 1) and Pea (Pis s 1) (50). An additional study confirmed that clinically relevant cross-reactivity between Pea and Peanut occurs and as a result of vicilin homologues (59).
Assessment of isoforms of the Lentil vicilin allergen, Len c 1.02, has been demonstrated to have a greater than 50% identity with Ara h 1 and Soybean conglutinin subunits (60). A protein of Lupine, a beta-conglutin precursor, was shown to be significantly homologous to Ara h 1 (61). Lupine has become a significant allergen as a result of its large-scale introduction into processed foods and frequent cross-reactions with other members of the legume family (61).
Nonetheless, cross-reactivity between vicilin proteins are not a certainty: although Cashew and Peanut vicilins share 27% identity, they do not share linear epitopes, and hence do not appear to be cross-reactive in spite of other similarities such as the presence of multiple linear IgE binding epitopes, a lack of any common primary structural characteristics of the linear IgE binding epitopes, positional overlap of some of the IgE binding epitopes, and the presence of immunodominant IgE binding epitopes (62).
One known IgE-binding epitope of Ara h 1 has been shown to have an 80% homology with the corresponding area of Ses i 3, a Sesame seed protein to which 75% of the Sesame-allergic patients are sensitized to (63).
Recombinant non-glycosylated protein produced in an E. coli strain carrying a cloned cDNA encoding Arachis hypogaea allergen Ara h 2
Common name: Conglutin
Biological function: 2S albumin trypsin inhibitor
Mw: 17.5 kDa
Ara h 2, a 2S albumin is homologous to and functions as a trypsin inhibitor, and is related to the 2S albumin superfamily of seed storage proteins (7,12,14,25,33,37,40,43-45,64-79). It is also known as Conglutin (12). Ara h 2 contributes up to 9% of the total protein content in peanut extracts (25). Ara h 2 is a 17.5 kDa protein and has a 30% homology with 2S albumins, but appears to have the closest homology with conglutin from Lupin. It does not appear to be made up of subunits like Jug r 1 or Ber e 1 (72,80). Ara h 2 has eight cysteine residues that could form up to four disulfide bonds (81).
Ara h 2 consists of two isoforms, namely Ara h 2.0101 and Ara h 2.0201. Ara h 2.0201 has similar but higher IgE binding than Ara h 2.0101 isoform (81% vs. 77%) and contains other IgE epitopes (73,82).
Ara h 2 is a protein that causes sensitization in >90% of patients with Peanut allergy (14,23-24,27,33-34,71). The prevalence of sensitization to a specific Peanut allergen varies between population groups (32).
Ara h 6 has homology to Ara h 2, especially in the middle part and at the C-terminal part of the protein. Almost complete inhibition of IgE-Ara h 6 interaction with Ara h 2 demonstrates that at least part of the epitopes of Ara h 6 are cross-reactive with epitopes on Ara h 2. Therefore Peanut-allergic patients recognize Ara h 6 both in vitro and in vivo to a similar extent as to that of Ara h 2 (15). However, Ara h 2 appears to be the more potent allergen, even though the two Peanut allergens share substantial cross-reactivity (7).
Ara h 2 (and the homologous Ara h 6) contains cores that are highly resistant to proteolytic digestion and to temperatures of up to 100 °C (7). This extreme immuno-logical stability of the core structures of Ara h 2 provides an explanation for the persistence of the allergenic potency even after food processing (7).
Roasting of Peanut was shown to cause a 3.6-fold increase in trypsin inhibitory activity, i.e., resistant to trypsin digestion and are more likely to remain intact in the gastrointestinal tract, and functional and structural comparison of the purified Ara h 2 from roasted Peanut to native and reduced Ara h 2 from raw Peanut showed that the roasted Ara h 2 mimics the behavior of native Ara h 2 in a partially reduced form (12). Furthermore, thermal treatment of rAra h 2 in the presence of reactive carbohydrates and carbohydrate breakdown products has been shown to induce a strong increase of the IgE-binding activity (69).
Digestion of Ara h 2 with trypsin, chymotrypsin, or pepsin results in a number of relatively large fragments that are resistant to further enzymatic digestion. These peptide fragments contain intact IgE- binding epitopes and several potential enzyme cut sites that are protected from the enzymes by the compact structure of the protein. Furthermore, the resistant protein fragments contain most of the immunodominant IgE-binding eptiopes (81). Furthermore, even though IgE antibody binding capacity is reduced by protease treatment, the mediator release from functional equivalent of mast cells or basophils, and the humanized RBL cell, demonstrated that the reduction in IgE antibody binding capacity did not necessarily translate into reduced allergenic potency (7).
Ara h 1 and Ara h 2 were also reported to bind higher levels of IgE and were more resistant to heat and digestion by gastrointestinal enzymes once they had undergone the Maillard reaction (58). Roasted Peanut from two different sources bound IgE from patients with Peanut allergy at approximately 90-fold higher levels than the raw Peanut from the same Peanut cultivars (58).
Greater than 75% of Peanut-allergic individuals are sensitised to Ara h 2 (14,29,33-34). In a Dutch study children with Peanut allergy recognized pre-dominantly Ara h 2 and Ara h 6, and the pattern remained stable over a period of time, whereas in Peanut-allergic adults, IgE was mainly directed to Ara h1 and Ara h2 (31).
Sensitisation and clinical effects of maternal peanut intake may occur soon after birth in breast-fed infants. Both major Peanut allergens Ara h 1 and Ara h 2 were detected (83).
Recombinant allergens may also play a role in the evaluation of cross-reactivity between plant families. Ara h 2 has a 30% homology with 2S albumins, but appears to have the closest homology with conglutin from Lupin (80). Cross-reactivity may therefore occur between Ara a 2 and other foods containing 2S albumins, dependent on the degree of homology. However, cross-reactivity is not a certainty. For example, conformational analysis of the linear IgE-binding epitopes mapped on the molecular surface of Ara h 2 showed no structural homology with the corresponding regions of the walnut Jug r 1, the pecan nut Car i 1 or the Brazil nut Ber e 1 allergens. This suggests that the cross-reactivity observed between these three may depend on other ubiquitous seed storage protein allergens, namely the vicilins. However, the major IgE-binding epitope identified on the molecular surface of the walnut Jug r 1 allergen shared a pronounced structural homology with the corresponding region of the pecan nut Car i 1 allergen. The authors concluded that with the exception of Peanut, 2S albumins could thus account for the IgE-binding cross-reactivity observed between some other dietary nuts, e.g. Walnut and Pecan nut (75).
Ara h 2 has been shown to share common IgE-binding epitopes with Almond and Brazil nut allergens (67).
Recombinant non-glycosylated protein produced in an E. coli strain carrying a cloned cDNA encoding Arachis hypogaea allergen Ara h 3
Common name: Glycinin
Biological function: 11S globulin trypsin inhibitor
Mw: 57 kDa
Ara h 3 is a glycinin, a member of the 11S globulin family, and may also function as a trypsin inhibitor (13,20,44,84-89). Ara h 3 was in first identified as a 14 kDa protein (90), but cloning revealed a 57 kDa protein that appears to be posttranslationally cleaved to smaller subunits (91).
Ara h 3 consists of a series of polypeptides ranging from approximately 14 to 45 kDa that can be classified as acidic and basic subunits, similar to the subunit organization of soy glycinin. Ara h 4 and Ara h 3 are considered to be the same allergen (13). Iso-allergens may be as a result of medication by post-translational cleavage (92).
A recent study also concluded, that Peanut-derived Ara h 3, in contrast to earlier reported recombinant Ara h 3, resembles, to a large extent, the molecular organization typical for proteins from the glycinin family. Posttranslational processing of Ara h 3 was shown to affect the IgE-binding properties and have impact on the allergenicity of Ara h 3 (13).
A comparison of the Peanut allergen sequences of Ara h 3/4, Ara h 3, Ara h 4 and Peanut trypsin inhibitor and the proteins Gly 1 and iso-Ara h 3 (not yet described as allergens), concluded that these proteins are isoallergens of each other, and that these isoallergens are post-translationally cleaved and held together by disulfide bonds in accordance to the 11S plant seed storage proteins signature (20).
The 11S globulins, also known as legumins, are classified into the Cupin superfamily, and are composed of 2 polypeptide chains of different molecular masses and amino acid sequences (heterodimeric form composed of a 20- to 40-kDa chain plus a 20- to 25-kDa chain), which are linked together by one disulfide bridge (93).
Between 20%-55% of Peanut-allergic individuals are sensitised to Ara h 3 (13,26,29,91). The prevalence of sensitization to a specific Peanut allergen varies between population groups (32). Ara h 3 was regarded as a minor allergen, but it was found that a group of Peanut-allergic Italian children were specifically sensitised to the basic subunit of Ara h 3. The authors stated their surprise that the dominant immunoreactivity in these patients was in a basic subunit of Ara h 3 because previous studies had indicated that Ara h 3 was only a minor Peanut allergen and that the identified allergenic epitopes occurred mainly in the acidic Ara h 3 subunit (88). It is therefore evident that sensitization to Ara h 3 depends on the population group studied and the methodology of the study, but there is a suggestion that the frequency of Ara h 3 sensitisation may indeed vary between population groups. In another study, recombinant Ara h 3 was recognized by IgE antibodies from approximately 45% of a Peanut-allergic patient population (91).
In a study that evaluated the pattern of IgE binding to specific Peanut allergens with the severity of clinical symptoms, 40 Peanut-allergic patients underwent a double-blind placebo-controlled low-dose Peanut challenge, during which the severity of the patients’ Peanut allergy was scored. Seventeen IgE binding bands were identified between 5 and 100 kDa with eight bound by >50% of patients and the total number of bands per patient correlated significantly with challenge score and serum IgE. However, two protein bands, identified as subunits of Ara h 3/4, had peak intensities that correlated positively with challenge score and a third band (Ara h 1) that correlated negatively. The study concluded that promiscuity of IgE binding appears more important than the recognition of individual proteins (30).
It has been argued that in contrast to recombinant Ara h 3, the allergen isolated from its native source is extensively proteolytically processed, and that native Ara h 3 polypeptides are much more complex than the recombinant protein used for epitope mapping experiments. The authors concluded that characterization of the allergenicity of Ara h 3 should therefore also include IgE-binding studies with Peanut-derived Ara h 3, providing the high degree of variation in the Ara h 3 protein structure, as this is what Peanut-allergic individuals are confronted with (94).
Ara h 3 is an 11S globulin and shares homology, and therefore varying degrees of cross-reactivity, with other 11S globulins. Sin a 2, a major allergen from Yellow mustard seed, was shown to have a sequence identity with other allergenic 11S globulins ranging between 27% and 38%. Three peptides described as epitopes in Ara h 3 were moderately conserved in Sin a 2 (95). Similarly, IgE-binding epitopes of Ara h 3 exhibited some structural homology among Peanut and tree nut allergens (Jug r 4 of Walnut, Cor a 9 of Hazelnut, Ana o 2 of Cashew nut) to account for the IgE-binding cross-reactivity observed. IgE-binding epitopes similar to those found in 11S globulin allergens do not apparently occur in other vicilin allergens with the cupin fold from Peanut (Ara h 1) or tree nuts (Jug r 2 of Walnut, Cor a 1 of Hazel nut, Ana o 3 of Cashew nut) (96).
Cross-reactivity has also been demonstrated between homologous Ara h 3 proteins (but not related) in Lupin (Lupin conglutin gamma) and Soybean (Soybean Bg7S) (97). A sequence similarity between Ara h 3 and the glycinins in Soybean and Pea of 62% to 72% has been reported (98).
Recombinant non-glycosylated protein produced in an E. coli strain strain carrying a cloned cDNA encoding Arachis hypogaea allergen Ara h 8
Common name: A Bet v 1-homologous allergen, Group 1 Fagales-related protein, PR-10 protein
Biological function: Plant defence protein, a pathogenesis-related protein
Mw: 17 kDa
Ara h 8 (14,27) is a Bet v 1-homologous panallergen. Ara h 8 appears to have a low stability to roasting and no stability to gastric digestion (14). A study was done of 9 Swiss and 11 Dutch patients with Peanut and Birch pollen allergy, and with positive double-blind, placebo-controlled food challenges to Peanut. All patients experienced symptoms of the oral cavity on exposure to Peanut; these progressed to more-severe symptoms in 40% of patients; serum IgE to recombinant Ara h 8 was detected in 85%. The study concluded that Peanut allergy may be mediated in a subgroup of patients by means of cross-reaction of Bet v 1 induced antibodies with the homologous Peanut allergen Ara h 8 (14).
Ara h 8 belongs to the PR-10 potein family. It has also been designated a Group 1 Fagales-related potein. Pathogenesis-related (PR) proteins of class 10 are abundant in higher plants. Some of these proteins are induced under stress conditions as part of the plant’s defence mechanism. Other homologues are developmentally regulated, and their expression varies in different plant organs. The PR-10 proteins are encoded by multigene families, have a weight of about 17 kDa and are found in the cytosol (28). They are common panallergens in Fagales pollens (Alder, Hornbeam, Beech, Chestnut) and may be present in a number of vegetables and fruits, e.g., Apple and Hazelnut. Pyr c 1, the major allergen from Pear (Pyrus communis), along with Lupine (Lupinus albus), is a homologous Bet v 1 allergen (29-30). Patients suffering from Birch pollen allergy can also exhibit allergic symptoms on exposure to the pollen of trees from the Fagales (Alder, Hazel, Hornbeam) and Oak and Chestnut, because all contain this panallergen. Recombinant marker allergens are therefore of value for more-accurate diagnoses and subsequent immunotherapy (31).
Due to cross-reactivity between Bet v 1 and Ara h 8, sensitisation to other PR-10 proteins might be evaluated to some extent using rAra h 8. For example, in a study that evaluated whether Fagales sensitisation occurred within a population not exposed to Birch pollen, reactivity to Bet v 1 was recorded in 84% of the Birch/Hazel/Oak co-reactivity group. Bet v 1 prevalence ranged between 48% and 21% among subgroups of patients coming from different areas (32).
Lupine is an emerging cause of food allergy, as a result of recent large-scale introduction into processed foods and frequent cross-reactions with other members of the legume family. Significant sequence homology and molecular similarity were found between the allergen Ara h 8 of Peanut and the pathogenesis-related protein PR-10 of White lupine (33).
Ara h 8 is also cross-reactive with Gly m 4 from Soya bean and Pru av 1 from Cherry. Nonetheless, although common binding epitopes do occur for this panallergen, patient-specific IgE epitope patterns also occur (29).
In a study evaluating severe oral allergy syndrome and anaphylactic reactions caused by a Bet v 1-related PR-10 protein in Soya bean, Gly m 4/SAM22, immediate-type allergic symptoms in patients with Birch pollen allergy after ingestion of Soy protein-containing food items were reported to occur from cross-reactivity of Bet v 1-specific IgE to homologous pathogenesis-related proteins, particularly the PR-10 protein Gly m 4/SAM22 (34). Similar cross-reactions can also be expected to Ara h 8.
Saavedra-Delgado AM. The many faces of the peanut. Allergy Proc 1989;10(4):291-4
Beyer K, Morrow E, Li XM, Bardina L, Bannon GA, Burks AW, Sampson HA. Effects of cooking methods on peanut allergenicity. J Allergy Clin Immunol 2001;107(6):1077-81
Mondoulet L, Paty E, Drumare MF, Ah-Leung S, Scheinmann P, Willemot RM, Wal JM, Bernard H. Influence of thermal processing on the allergenicity of peanut proteins.
J Agric Food Chem 2005;53(11):4547-53
Kang IH, Gallo M, Tillman BL Distribution of allergen composition in peanut (Arachis hypogaea l.) and wild progenitor (Arachis) species. Crop Science 2007;47(3):997-1003
Bohle B, Swoboda I, Spitzauer S, et al. Food Antigens: structure and function. In Metcalf DD, Sampson HA, Simon RA, editors. Food Allergy: Adverse reactions to Foods and Food Additives.
Blackwell Scientific Publications 2003:38-50
Loza C, Brostoff J Peanut allergy.
Clin Exp Allergy 1995;25(6):493-502
Lehmann K, Schweimer K, Reese G, Randow S, Suhr M, Becker WM, Vieths S, Rosch P. Structure and stability of 2S albumin-type peanut allergens: implications for the severity of peanut allergic reactions.
Biochem J 2006 May 1;395(3):463-72
Dean TP. Immunological responses in peanut allergy. [Editorial]
Clin Exp Allergy 1998;28:7-9
Scurlock AM, Burks AW. Peanut allergenicity. Ann Allergy Asthma Immunol 2004;93(5 Suppl 3):S12-8
Koppelman SJ, Vlooswijk RA, Knippels LM, Hessing M, Knol EF, van Reijsen FC, Bruijnzeel-Koomen CA. Quantification of major peanut allergens Ara h 1 and Ara h 2 in the peanut varieties Runner, Spanish, Virginia, and Valencia, bred in different parts of the world. Allergy 2001 Feb;56(2):132-7
Wichers HJ, De Beijer T, Savelkoul HF, Van Amerongen A. The major peanut allergen Ara h 1 and its cleaved-off N-terminal peptide; possible implications for peanut allergen detection.
J Agric Food Chem 2004;52(15):4903-7
Maleki SJ, Viquez O, Jacks T, Dodo H, Champagne ET, Chung SY, Landry SJ. The major peanut allergen, Ara h 2, functions as a trypsin inhibitor, and roasting enhances this function. J Allergy Clin Immunol 2003;112(1):190-5
Koppelman SJ, Knol EF, Vlooswijk RA, Wensing M, Knulst AC, Hefle SL, Gruppen H, Piersma S. Peanut allergen Ara h 3: isolation from peanuts and biochemical characterization. Allergy 2003;58(11):1144-51
Kleber-Janke T, Crameri R, Appenzeller U, Schlaak M, Becker WM Selective cloning of peanut allergens, including profilin and 2S albumins, by phage display technology. Int Arch Allergy Immunol 1999;119:265-74
Koppelman SJ, de Jong GA, Laaper-Ertmann M, Peeters KA, Knulst AC, Hefle SL, Knol EF. Purification and immunoglobulin E-binding properties of peanut allergen Ara h 6: evidence for cross-reactivity with Ara h 2. Clin Exp Allergy 2005;35(4):490-7
Mittag D, Akkerdaas J, Ballmer-Weber BK, Vogel L, Wensing M, Becker WM,
Koppelman SJ, Knulst AC, Helbling A, Hefle SL, Van Ree R, Vieths S. Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in patients with combined birch pollen and peanut allergy.
J Allergy Clin Immunol 2004;114(6):1410-7
Burks AW, Cockrell G, Connaughton C, Guin J, Allen W, Helm RM. Identification of peanut agglutinin and soybean trypsin inhibitor as minor legume allergens. Int Arch Allergy Immunol 1994;105(2):143-9
Asero R, Mistrello G, Roncarolo D, Amato S, Caldironi G, Barocci F, Van Ree R. Immunological cross-reactivity between lipid transfer proteins from botanically unrelated plant-derived foods: a clinical study.
Pons L, Chery C, Romano A, Namour F, Artesani MC, Gueant JL. The 18 kDa peanut oleosin is a candidate allergen for IgE-mediated reactions to peanuts.
Allergy 2002;57 Suppl 72:88-93
Boldt A, Fortunato D, Conti A, Petersen A, Ballmer-Weber B, Lepp U, Reese G, Becker WM. Analysis of the composition of an immunoglobulin E reactive high molecular weight protein complex of peanut extract containing Ara h 1 and Ara h 3/4.
Pomes A, Helm RM, Bannon GA, Burks AW, Tsay A, Chapman MD. Monitoring peanut allergen in food products by measuring Ara h 1. J Allergy Clin Immunol 2003;111(3):640-5
Burks AW, Sampson HA, Bannon GA. Review article series II: peanut allergens.
Bernard H, Paty E, Mondoulet L, Burks AW, Bannon GA, Wal JM, Scheinmann P. Serological characteristics of peanut allergy in children. Allergy 2003;58(12):1285-92
Clarke MC, Kilburn SA, Hourihane JO, Dean KR, Warner JO, Dean TP. Serological characteristics of peanut allergy.
Clin Exp Allergy 1998;28(10):1251-7
de Jong EC, Van Zijverden M, Spanhaak S, Koppelman SJ, Pellegrom H, Penninks AH. Identification and partial characterization of multiple major allergens in peanut proteins. Clin Exp Allergy 1998;28(6):743-51
Koppelman SJ, Wensing M, Ertmann M, Knulst AC, Knol EF. Relevance of Ara h1, Ara h2 and Ara h3 in peanut-allergic patients, as determined by immunoglobulin E Western blotting, basophil-histamine release and intracutaneous testing: Ara h2 is the most important peanut allergen.
Clin Exp Allergy 2004 Apr;34(4):583-90
Stanley JS, Bannon GA. Biochemistry of food allergens. Clin Rev Allergy Immunol 1999;17(3):279-91
Martinez A, Asturias JA, Monteseirin J, Moreno V, Garcia-Cubillana A, Hernandez M, de la Calle A, Sanchez-Hernandez C, Perez-Formoso JL, Conde J. The allergenic relevance of profilin (Ole e 2) from Olea europaea pollen.
Allergy 2002;57 Suppl 71:17-23
Shreffler WG, Beyer K, Chu TH, Burks AW, Sampson HA. Microarray immunoassay: association of clinical history, in vitro IgE function, and heterogeneity of allergenic peanut epitopes. J Allergy Clin Immunol 2004;113(4):776-82
Lewis SA, Grimshaw KE, Warner JO, Hourihane JO. The promiscuity of immunoglobulin E binding to peanut allergens, as determined by Western blotting, correlates with the severity of clinical symptoms.
Clin Exp Allergy 2005;35(6):767-73
Flinterman AE, van HE, den Hartog Jager CF, Koppelman S, Pasmans SG, Hoekstra MO, Bruijnzeel-Koomen CA, Knulst AC, Knol EF. Children with peanut allergy recognize predominantly Ara h2 and Ara h6, which remains stable over time.
Clin Exp Allergy 2007;37(8):1221-8
Kang IH, Srivastava P, Ozias-Akins P, Gallo M Temporal and spatial expression of the major allergens in developing and germinating peanut seed.
Plant Physiol 2007;144(2):836-45
Astier C, Morisset M, Roitel O, Codreanu F, Jacquenet S, Franck P, Ogier V, et al. Predictive value of skin prick tests using recombinant allergens for diagnosis of peanut allergy. J Allergy Clin Immunol 2006;118(1):250-6
Peeters KA, Koppelman SJ, van HE, van der Tas CW, den Hartog Jager CF, Penninks AH, Hefle SL, Bruijnzeel-Koomen CA, Knol EF, Knulst AC. Does skin prick test reactivity to purified allergens correlate with clinical severity of peanut allergy?
Clin Exp Allergy 2007;37(1):108-15
Beyer K, Ellman-Grunther L, Jarvinen KM, Wood RA, Hourihane J, Sampson HA. Measurement of peptide-specific IgE as an additional tool in identifying patients with clinical reactivity to peanuts.
J Allergy Clin Immunol 2003;112(1):202-7
Viquez OM, Konan KN, Dodo HW. Structure and organization of the genomic clone of a major peanut allergen gene, Ara h 1.
Mol Immunol 2003;40(9):565-71
Kleber-Janke T, Becker WM. Use of modified BL21(DE3) Escherichia coli cells for high-level expression of recombinant peanut allergens affected by poor codon usage. Protein Expr Purif 2000;19(3):419-24
Stanley JS, Helm RM, Cockrell G, Burks AW, Bannon GA. Peanut hypersensitivity. IgE binding characteristics of a recombinant Ara h I protein.
Adv Exp Med Biol 1996;409:213-6
Burks AW, Cockrell G, Stanley JS, Helm RM, Bannon GA. Recombinant peanut allergen Ara h I expression and IgE binding in patients with peanut hypersensitivity.
J Clin Invest 1995;96(4):1715-21
Becker W-M, Kleber-Janke T, Lepp U. Four novel recombinant peanut allergens: more information, more problems.
Int Arch Allergy Immun 2001;124:100-2
Shreffler WG, Castro RR, Kucuk ZY, Charlop-Powers Z, Grishina G, Yoo S, Burks AW, Sampson HA. The major glycoprotein allergen from Arachis hypogaea, Ara h 1, Is a ligand of dendritic cell-specific ICAM-grabbing nonintegrin and acts as a Th2 adjuvant in vitro. J Immunol 2006;177(6):3677-85
Chatel JM, Song L, Bhogal B, Orson FM. Various factors (allergen nature, mouse strain, CpG/recombinant protein expressed) influence the immune response elicited by genetic immunization.
Li XM, Srivastava K, Huleatt JW, Bottomly K, Burks AW, Sampson HA. Engineered recombinant peanut protein and heat-killed Listeria monocytogenes coadministration protects against peanut-induced anaphylaxis in a murine model.
J Immunol 2003;170(6):3289-95
International Union of Immunological Societies Allergen Nomenclature: IUIS official list http://www.allergen.org/List.htm 2006
Palmer GW, Dibbern DA Jr, Burks AW, Bannon GA, Bock SA, Porterfield HS, McDermott RA, Dreskin SC. Comparative potency of Ara h 1 and Ara h 2 in immunochemical and functional assays of allergenicity.
Clin Immunol 2005;115(3):302-12
Burks AW, Cockrell G, Connaughton C, Helm RM. Epitope specificity and immunoaffinity purification of the major peanut allergen, Ara h I.
J Allergy Clin Immunol 1994;93(4):743-50
Maleki SJ, Kopper RA, Shin DS, Park CW, Compadre CM, Sampson H, Burks AW, Bannon GA. Structure of the major peanut allergen Ara h 1 may protect IgE-binding epitopes from degradation.
J Immunol 2000;164(11):5844-9
Yan YS, Lin XD, Zhang YS, Wang L, Wu K, Huang SZ Isolation of peanut genes encoding arachins and conglutins by expressed sequence tags.
Plant Sci 2005;169(2):439-45
van Boxtel EL, van Beers MMC, Koppelman SJ, van den Broek LAM, Gruppen H.
Allergen Ara h 1 occurs in peanuts as a large oligomer rather than as a trimer.
J Agric Food Chem 2006;54(19):7180-6
Barre A, Borges JP, Rougé P. Molecular modelling of the major peanut allergen Ara h 1 and other homotrimeric allergens of the cupin superfamily: a structural basis for their IgE-binding cross-reactivity.
Burks AW, Shin D, Cockrell G, Stanley JS, Helm RM, Bannon GA. Mapping and mutational analysis of the IgE-binding epitopes on Ara h 1, a legume vicilin protein and a major allergen in peanut hypersensitivity.
Eur J Biochem 1997;245(2):334-9
Koppelman SJ, Bruijnzeel-Koomen CA, Hessing M, de Jongh HH. Heat-induced conformational changes of Ara h 1, a major peanut allergen, do not affect its allergenic properties.
J Biol Chem 1999;274(8):4770-7
Shin DS, Compadre CM, Maleki SJ, Kopper RA, Sampson H, Huang SK, Burks AW, Bannon GA. Biochemical and structural analysis of the IgE binding sites on Ara h1, an abundant and highly allergenic peanut protein.
J Biol Chem 1998;273(22):13753-9
Buschmann L, Petersen A, Schlaak M, Becker WM. Reinvestigation of the major peanut allergen Ara h 1 on molecular level. Monogr Allergy 1996;32:92-8
Burks AW, Williams LW, Helm RM, Connaughton C, Cockrell G, O’Brien T. Identification of a major peanut allergen, Ara h 1, in patients with atopic dermatitis and positive peanut challenges.
J Allergy Clin Immunol 1991;88:172-9
Chassaigne H, Brohee M, Norgaard JV, van Hengel AJ. Investigation on sequential extraction of peanut allergens for subsequent analysis by ELISA and 2D gel electrophoresis.
Food Chem 2007;105(4):1671-81
Eiwegger T, Rigby N, Mondoulet L, Bernard H, Krauth MT, Boehm A, Dehlink E, Valent P, Wal JM, Mills EN, Szepfalusi Z. Gastro-duodenal digestion products of the major peanut allergen Ara h 1 retain an allergenic potential.
Clin Exp Allergy 2006;36(10):1281-8
Maleki SJ, Chung SY, Champagne ET, Raufman JP. The effects of roasting on the allergenic properties of peanut proteins.
J Allergy Clin Immunol 2000;106(4):763-8
Wensing M, Knulst AC, Piersma S, O’kane F, Knol EF, Koppelman SJ. Patients with anaphylaxis to pea can have peanut allergy caused by cross-reactive IgE to vicilin (Ara h 1). J Allergy Clin Immunol 2003;111(2):420-4
Lopez-Torrejon G, Salcedo G, Martin-Esteban M, Diaz-Perales A, Pascual CY, Sanchez-Monge R. Len c 1, a major allergen and vicilin from lentil seeds: protein isolation and cDNA cloning. J Allergy Clin Immunol 2003;112(6):1208-15
Guarneri F, Guarneri C, Benvenga S. Identification of potentially cross-reactive peanut-lupine proteins by computer-assisted search for amino acid sequence homology.
Int Arch Allergy Immunol 2005;138(4):273-7
Wang F, Robotham JM, Teuber SS, Tawde P, Sathe SK, Roux KH. Ana o 1, a cashew (Anacardium occidental) allergen of the vicilin seed storage protein family.
J Allergy Clin Immunol 2002;110(1):160-6
Beyer K, Bardina L, Grishina G, Sampson HA. Identification of sesame seed allergens by 2-dimensional proteomics and Edman sequencing: Seed storage proteins as common food allergens. J Allergy Clin Immunol 2002;110(1):154-9
Lehmann K, Hoffmann S, Neudecker P, Suhr M, Becker WM, Rosch P. High-yield expression in Escherichia coli, purification, and characterization of properly folded major peanut allergen Ara h 2.
Protein Expr Purif 2003;31(2):250-9
Viquez OM, Summer CG, Dodo HW. Isolation and molecular characterization of the first genomic clone of a major peanut allergen, Ara h 2. J Allergy Clin Immunol 2001;107(4):713-7
Becker WM, Suhr M, Lindner B, Wicklein D, Lepp U. Reinvestigation of the major peanut allergen Ara h 2 on molecular level. [Poster: XXI Congress of EAACI] Allergy 2002;57 Suppl 73:79-84
de Leon MP, Drew AC, Glaspole IN, Suphioglu C, O’Hehir RE, Rolland JM. IgE cross-reactivity between the major peanut allergen Ara h 2 and tree nut allergens.
Mol Immunol 2007;44(4):463-71
Glenting J, Poulsen LK, Kato K, Madsen SM, Frokiaer H, Wendt C, Sorensen HW. Production of Recombinant Peanut Allergen Ara h 2 using Lactococcus lactis.
Microb Cell Fact 2007;6(1):28
Gruber P, Becker WM, Hofmann T. Influence of the maillard reaction on the allergenicity of rAra h 2, a recombinant major allergen from peanut (arachis hypogaea), its major epitopes, and peanut agglutinin.
J Agric Food Chem 2005;53(6):2289-96
Kleber-Janke T, Becker W-M: High-level expression of peanut allergens affected by rare codon usage. Strategies 2000;13:74-5
Burks AW, Williams LW, Connaughton C, Cockrell G, O’Brien TJ, Helm RM. Identification and characterization of a second major peanut allergen, Ara h II, with use of the sera of patients with atopic dermatitis and positive peanut challenge.
J Allergy Clin Immunol 1992;90(6 Pt 1):962-9
Stanley JS, King N, Burks AW, Huang SK, Sampson H, Cockrell G, Helm RM, West CM, Bannon GA. Identification and mutational analysis of the immunodominant IgE binding epitopes of the major peanut allergen Ara h 2. Arch Biochem Biophys 1997;342(2):244-53
Hales BJ, Bosco A, Mills KL, Hazell LA, Loh R, Holt PG, Thomas WR. Isoforms of the major peanut allergen Ara h 2: IgE binding in children with peanut allergy. Int Arch Allergy Immunol 2004 2;135(2):101-7
Shreffler WG, Lencer DA, Bardina L, Sampson HA. IgE and IgG4 epitope mapping by microarray immunoassay reveals the diversity of immune response to the peanut allergen, Ara h 2.
J Allergy Clin Immunol 2005;116(4):893-9
Barre A, Borges JP, Culerrier R, Rouge P. Homology modelling of the major peanut allergen Ara h 2 and surface mapping of IgE-binding epitopes.
Immunol Lett 2005;100(2):153-8
Schein CH, Ivanciuc O, Braun W. Common physical-chemical properties correlate with similar structure of the IgE epitopes of peanut allergens.
J Agric Food Chem 2005;53(22):8752-9
Glaspole IN, de Leon MP, Rolland JM, O’hehir RE. Characterization of the T-cell epitopes of a major peanut allergen, Ara h 2. Allergy 2005;60(1):35-40
McDermott RA, Porterfield HS, Mezayen RE, Burks AW, Pons L, Schlichting DG, Solomon B, Redzic JS, Harbeck RJ, Duncan MW, Hansen KC, Dreskin SC. Contribution of
Ara h 2 to peanut-specific, immunoglobulin E-mediated, cell activation.
Clin Exp Allergy 2007;37(5):752-63
Burks AW, Cockrell G, Connaughton C, Karpas A, Helm RM. Epitope specificity of the major peanut allergen, Ara h II.
J Allergy Clin Immunol 1995;95(2):607-11
Teuber SS, Dandekar AM, Peterson WR, Sellers CL. Cloning and sequencing of a gene encoding a 2S albumin seed storage protein precursor from English walnut (Juglans regia), a major food allergen. J Allergy Clin Immunol 1998;101(6 Pt 1):807-14
Sen M, Kopper R, Pons L, Abraham EC, Burks AW, Bannon GA. Protein structure plays a critical role in peanut allergen stability and may determine immunodominant IgE-binding epitopes.
J Immunol 2002;169(2):882-7
Chatel JM, Bernard H, Orson FM. Isolation and Characterization of Two Complete Ara h 2 Isoforms cDNA.
Int Arch Allergy Immunol 2003;131(1):14-8
Vadas P, Wai Y, Burks W, Perelman B. Detection of peanut allergens in breast milk of lactating women.
Dodo HW, Viquez OM, Maleki SJ, Konan KN. cDNA clone of a putative peanut (Arachis hypogaea L.) trypsin inhibitor has homology with peanut allergens Ara h 3 and Ara h 4.
J Agric Food Chem 2004;52(5):1404-9
Rabjohn P, West CM, Connaughton C, Sampson HA, Helm RM, Burks AW, Bannon GA. Modification of Peanut Allergen Ara h 3: Effects on IgE Binding and T Cell Stimulation.Int Arch Allergy Immunol 2002;128(1):15-23
Kang IH, Gallo M Cloning and characterization of a novel peanut allergen Ara h 3 isoform displaying potentially decreased allergenicity.
Plant Sci 2006;172(2):345-53
Xiang P, Beardslee TA, Zeece MG, Markwell J, Sarath G. Identification and analysis of a conserved immunoglobulin E-binding epitope in soybean G1a and G2a and peanut Ara h 3 glycinins.
Arch Biochem Biophys 2002;408(1):51-7
Restani P, Ballabio C, Corsini E, Fiocchi A, Isoardi P, Magni C, Poiesi C, Terracciano L, Duranti M. Identification of the basic subunit of Ara h 3 as the major allergen in a group of children allergic to peanuts. Ann Allergy Asthma Immunol 2005;94(2):262-6
Beyer K, Grishina G, Bardina L, Grishin A, Sampson HA. Identification of an 11S globulin as a major hazelnut food allergen in hazelnut-induced systemic reactions.
J Allergy Clin Immunol 2002;110(3):517-23
Eigenmann PA, Burks AW, Bannon GA, Sampson HA. Identification of unique peanut and soy allergens in sera adsorbed with cross-reacting antibodies. J Allergy Clin Immunol 1996;98(5 Pt 1):969-78
Rabjohn P, Helm EM, Stanley JC, West CM, Sampson HA, Burks AW, et al. Molecular cloning and epitope analysis of the peanut allergen Ara h 3.
J Clin Invest 1999;103:535-42
Liang XQ, Luo M, Holbrook CC, Guo BZ Storage protein profiles in Spanish and runner market type peanuts and potential markers. BMC Plant Biol 2006; 6(1):24
Rodin J, Sjodahl S, Josefsson LG, Rask L. Characterization of a Brassica napus gene encoding a cruciferin subunit: estimation of sizes of cruciferin gene families.
Plant Mol Biol 1992;20(3):559-63
Piersma SR, Gaspari M, Hefle SL, Koppelman SJ. Proteolytic processing of the peanut allergen Ara h 3.
Mol Nutr Food Res 2005;49(8):744-55
Palomares O, Vereda A, Cuesta-Herranz J, Villalba M, Rodriguez R. Cloning, sequencing, and recombinant production of Sin a 2, an allergenic 11S globulin from yellow mustard seeds. J Allergy Clin Immunol 2007;119(5):1189-96
Barre A, Jacquet G, Sordet C, Culerrier R, Rouge P. Homology modelling and conformational analysis of IgE-binding epitopes of Ara h 3 and other legumin allergens with a cupin fold from tree nuts. Mol Immunol 2007;44(12):3243-55
Magni C, Ballabio C, Restani P, Sironi E, Scarafoni A, Poiesi C, Duranti M. Two-dimensional electrophoresis and western-blotting analyses with anti Ara h 3 basic subunit IgG evidence the cross-reacting polypeptides of Arachis hypogaea, Glycine max, and Lupinus albus seed proteomes.
J Agric Food Chem 2005;53(6):2275-81
Beardslee TA, Zeece MG, Sarath G, Markwell JP. Soybean glycinin G1 acidic chain shares IgE epitopes with peanut allergen Ara h 3. Int Arch Allergy Immunol 2000;123(4):299-307