The Journal of Allergy and Clinical Immunology
Volume 113, Issue 5 , Pages 821-830, May 2004

A classification of plant food allergens☆

  • Heimo Breiteneder, PhD

      Affiliations

    • Corresponding Author InformationReprint requests: Heimo Breiteneder, PhD, Department of Pathophysiology, Medical University of Vienna, AKH-EBO-3Q, Waehringer Guertel 18-20, 1090 Vienna, Austria.
    • ,
  • Christian Radauer, PhD

From the Department of Pathophysiology, Medical University of Vienna Austria

Received 28 November 2003; received in revised form 28 January 2004; accepted 28 January 2004.

Vienna, AustriaThis activity is available for CME credit. See page 34A for important information.

Article Outline

Abstract 

Plant food allergens can be classified into families and superfamilies on the basis of their structural and functional properties. The most widespread groups of plant proteins that contain allergens are the cupin and prolamin superfamilies and the protein families of the plant defense system. The cupin superfamily includes allergenic seed storage proteins of the vicilin and legumin type present in soybeans, peanuts, and tree nuts. The prolamin superfamily includes several important types of allergens of legumes, tree nuts, cereals, fruits, and vegetables, such as the 2S albumin seed storage proteins, the nonspecific lipid transfer proteins, and the cereal α-amylase and protease inhibitors. Plant food allergens are also found among the various groups of defense proteins that enable plants to resist biotic and abiotic stress, such as the pathogenesis-related proteins, certain proteases, and protease inhibitors. This review focuses on a classification system of plant food allergens that is emerging from the synopsis of allergology and protein evolution.

Keywords:  Plant food allergen, cupin, prolamin, vicilin, legumin, 2S albumin, nonspecific lipid transfer protein, α-amylase/trypsin inhibitor, cereal prolamin, pathogenesis-related protein, protease, protease inhibitor, profilin

Abbreviations:  nsLTP, Nonspecific lipid transfer protein, PR, Pathogenesis-related protein, TLP, Thaumatin-like protein

 

Plant tissues that are consumed by humans contain thousands of different proteins. The maximum number of different genes expressed at mid endosperm development of wheat, for example, was estimated to be within the range of 4500 to 8000.1 The number of proteins of any given allergen source capable of eliciting an allergic response in atopic individuals is several orders of magnitudes lower. In recent years, there has been a trend toward bringing order to the various allergens. The most obvious system was to classify allergens by their source, which had been done, for example, by the International Union of Immunological Societies Allergen Nomenclature Subcommittee (http://www.allergen.org). Proposals were made to classify plant food allergens by their biologic function,2 by their protein fold,3 or by protein families.4., 5., 6.

The most natural classification system might well be based on both structural and functional properties of proteins. The information present in the protein databases challenges the molecular allergologist to apply this knowledge to the classification of allergens.7 Proteins are clustered together into families if they have residue identities of 30% or greater or if they have lower sequence identities but their functions and structures are very similar.8., 9. Families whose members have low sequence identities but whose structures and functional features suggest a probable common evolutionary origin are placed together in superfamilies.8., 9.

Most plant food allergens belong to a few protein families and superfamilies. Many allergens belong to the cupin superfamily (7S and 11S seed storage proteins) or the prolamin superfamily (2S albumins, nonspecific lipid transfer proteins [nsLTPs], α-amylase/trypsin inhibitors, and prolamin storage proteins of cereals; Table I). The pathogenesis-related proteins (PRs) represent a heterogeneous collection of 14 plant protein families that are involved in plant resistance to pathogens or adverse environmental conditions.10 Many plant food allergens are homologous to PRs (Table II).2., 11. Storage proteins are the cause of well-known allergic reactions to peanuts and cereals.4 PRs are responsible for pollen-fruit or latex-fruit cross-reactive syndromes.12., 13. In addition, there are some unrelated families of structural and metabolic plant proteins that harbor allergenic proteins, such as the profilins (Table III).14

Table I. Allergens from the cupin and prolamin superfamilies
Protein familyExamples
Cupin superfamily
VicilinsAra h 1 (peanut), Jug r 2 (walnut)
LeguminsAra h 3/4 (peanut), Cor a 9 (hazelnut)
Prolamin superfamily
2S albuminsBer e 1 (Brazil nut), Ses i 2 (sesame)
nsLTPsPru p 3 (peach), Cor a 8 (hazelnut)
Cereal α-amylase/protease inhibitorsRice dimeric alpha-amylase inhibitor
Cereal prolaminsTri a 19 (wheat), Sec c 20 (rye)
Table II. Allergens from the plant defense system
Protein familyExamples
PRs
PR-2: endo-β1, 3-glucanasesBanana glucanase
PR-3: class I chitinasesPers a 1 (avocado), Cas s 5 (chestnut)
PR-4: Win-like proteinsBra r 2 (turnip)
PR-5: TLPsPru av 2 (cherry), Mal d 2 (apple)
PR-9: peroxidasesTri a Bd 36K (wheat)
PR-10: intracellular PR-proteinsApi g 1 (celery), Mal d 1 (apple)
PR-14: nsLTPsSee Table I
Proteases
Papain-like cysteine proteasesAct c 1 (kiwi), Gly m Bd 30K (soybean)
Subtilisin-like serine proteasesCuc m 1 (melon)
Protease inhibitors
Kunitz-type protease inhibitorsSoybean trypsin inhibitor
Cereal α-amylase/protease inhibitorsSee Table I
Table III. Other allergenic structural and metabolic proteins
Protein familyExamples
Structural proteins
ProfilinsApi g 4 (celery), Pru av 4 (cherry)
OleosinsPeanut oleosin
Storage proteins
PatatinSola t 1 (potato)
Enzymes
Phenylcoumaran benzylic ether reductasesPyr c 5 (pear)
CyclophilinsCarrot cyclophilin
β-FructofuranosidasesLyc e 2 (tomato)
Flavin adenine dinucleotide-dependent oxidasesApi g 5 (celery)

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1. The cupin superfamily 

The cupins are a functionally diverse superfamily of proteins that share 2 short conserved consensus sequence motifs and a β-barrel structural core domain to which the term cupin (Latin cupa, a barrel) was given.15 Single-domain cupins contain one (Fig 1, A) and bicupins contain 2 such conserved cupin domains (Fig 1, B and C). Bicupins include the globulin seed storage proteins that are major components of the human diet. The globulins have been studied in most detail in legumes, in particular soy and peanut. On the basis of their sedimentation coefficient, the globulins can be divided into the 7S vicilin-type globulins (Fig 1, B and D) and the 11S legumin-type globulins (Fig 1, C and E).

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  • FIG 1. 

    Structures of proteins from the cupin superfamily. A, Barley germin monomer (Protein Data Bank accession no. 1FIZ), a protein containing one cupin domain. B, Single subunit of soybean β-conglycinin, a vicilin (1IPK). C, Single subunit of soybean proglycinin, a legumin (1FXZ). D and E, Molecular surfaces of the trimers of β-conglycinin and proglycinin. Blue, α-helices; red, β-strands; yellow, disulfide bonds; green, manganese ion.

1.1. Vicilins 

Mature 7S globulins are trimeric proteins of about 150 to 190 kd. The molecular weights of the subunits range from about 40 to 80 kd. Vicilins lack cysteines and therefore contain no disulfide bonds.16 The 3-dimensional structures of the 7S globulins canavalin from jack bean,17., 18. phaseolin from French bean,19 and the β subunit of β-conglycinin from soybean20 (Fig 1, B and D) have been determined. These structures illustrate that trimeric vicilins are disk shaped.

The best-analyzed allergenic vicilin is the major peanut allergen Ara h 1, which is responsible for the majority of cases of fatal anaphylaxis induced by a plant food.21 Three Ara h 1 monomers assemble to form a highly stable trimeric complex that gives the molecule some protection from protease digestion and denaturation and allows its passage across the small intestine.22 The majority of the B-cell epitopes of Ara h 1 are located in the areas of the subunit-subunit contacts that are protected from protease degradation.23 In soybean approximately 50% of the 7S fraction of its seed storage globulins consist of β-conglycinin, a 180-kd glycoprotein. β-Conglycinin trimers are composed of 3 subunits, α, α′, and β, in various combinations. The α subunit, Gly m Bd 60K, is one of the major allergenic proteins in the soybean 7S-globulin fraction.24 The allergen Len c 1 from lentils was identified as a γ-vicilin subunit.25

A survey suggested that 0.5% of the US population is afflicted by various degrees of nut allergy.26 Jug r 2 is an allergenic vicilin from English walnuts, which are often implicated in life-threatening nut allergy.27 The linear IgE epitopes of the allergenic vicilins Ana o 1 from cashew and Ara h 1 from peanut do not show significant sequence conservation,28 explaining the lack of cross-reactivity between peanut- and tree nut–reactive patient sera.29 The sensitization rate to sesame seeds in Australia is one third of that of peanut allergy and higher than that to any tree nut.30 Ses i 3 from sesame seeds is an allergenic 7S vicilin-type globulin.31

1.2. Legumins 

Mature 11S globulins are hexameric proteins that are initially assembled and transported through the secretory system as intermediate trimers.16 In the protein storage vacuole, each subunit of the trimer is proteolytically cleaved to yield an acidic 30- to 40-kd polypeptide linked by a disulfide bond to a basic polypeptide of approximately 20 kd. Cleavage is accompanied by the transformation of 2 trimers into a mature hexameric 11S globulin.32 The 3-dimensional structure of proglycinin from soybean, an 11S globulin precursor, has been determined (Fig 1, C and E).33

Ara h 3 was identified as the N-terminal portion of a peanut glycinin subunit, an 11S legumin-like seed storage protein.34 Ara h 3 and Ara h 4, previously described as distinct peanut allergens with high sequence similarity to glycinins, are now considered to be the same allergen.35 The structure of Ara h 3 is similar to that of soybean glycinin, and both the basic and the acidic chain of each subunit can bind IgE from individuals with peanut allergy.35 The 11S fraction of soybean proteins consists almost entirely of glycinin, the predominant soy storage globulin. Native glycinin is a 350-kd hexamer composed of different combinations of the 5 subunits G1 to G5. IgE epitopes of the acidic chain of G1 have been found to be similar to IgE epitopes of the peanut glycinin Ara h 3.36 Each basic chain of the 5 soybean glycinin subunits reacted with IgE from individuals with soybean allergy.37

Hazelnuts are commonly consumed tree nuts that can induce allergic reactions. Cor a 9 is an allergenic hazelnut 11S globulin that is not linked to a pollen allergy.38 Allergic reactions to cashew nuts, although relatively infrequent, can be life-threatening. Ana o 2 was identified as a major legumin-like cashew allergen.39 Additional 11S allergenic plant food globulins were identified in coconut and walnut40 and in almond.41

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2. The prolamin superfamily 

The existence of this superfamily was proposed on the basis of the presence of a conserved skeleton of 8 cysteine residues within the proteins' sequences.42 This superfamily is named after the cereal prolamins, the major storage proteins of cereal grains (with the exception of oats and rice), which are characterized by their high contents of proline and glutamine.5 In addition to the cereal prolamins, the broader definition of the superfamily now includes several important plant allergen families, 2S albumin seed storage proteins (Fig 2, A), nsLTPs (Fig 2, B), and cereal seed inhibitors of α-amylase, trypsin, or both (Fig 2, C). All of these low-molecular-weight proteins are cysteine rich and have similar 3-dimensional structures that are rich in α-helices. The soybean hydrophobic protein (Fig 2, D) that is responsible for respiratory allergy to soybeans also possesses the characteristic 8-cysteine residue skeleton and a similar conformation.43., 44.

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  • FIG 2. 

    Secondary structures of allergens from the prolamin superfamily. A, Rapeseed 2S albumin (napin BNIb, Protein Data Bank accession no. 1PNB). B, Barley nsLTP (1LIP). C, Wheat α-amylase inhibitor (1HSS). D, Soybean hydrophobic seed protein (1HYP). Blue, α-helices; red, β-strands; yellow, disulfide bonds.

2.1. 2S albumins 

The 2S albumins are a major group of storage proteins present in many dicotyledonous plant species.16 Typical 2S albumins, such as the Brazil nut 2S albumin, are heterodimeric proteins that consist of 2 polypeptide chains of approximately 4 and 9 kd that are held together by 4 disulfide bonds (Fig 2, A).16

Several of the tree nut and seed allergens are 2S albumins. They include Ber e 1 from Brazil nut,45., 46. Jug r 1 from the English walnut,47 and 2S albumins from cashew nuts.48 Ses i 2 is the clinically most important allergen of sesame seeds.31., 49. The proteins responsible for allergic reactions to mustard were identified as the 2S albumins Sin a 1 from yellow mustard seeds50 and Bra j 1 from oriental mustard seeds.51 Ara h 2, 6, and 7 belong to the conglutin protein family, which is related to the 2S albumin family.52 Ara h 2 was found to act as a weak trypsin inhibitor that protects Ara h 1 from degradation by trypsin.53

2.2. Nonspecific lipid transfer proteins 

The family of nsLTPs comprises 7- to 9-kd monomeric proteins that are held together by 4 disulfide bonds to form a hydrophobic tunnel (Fig 2, B).54 nsLTPs have a broad substrate-binding specificity.55 They usually accumulate in the outer epidermal layers of plant organs, thus explaining the stronger allergenicity of peels compared with pulps of Rosaceae fruits.56 nsLTPs are resistant to proteolysis, harsh pH changes, or thermal treatments and can refold to their native structure on cooling.56 Their common structural features are the basis of their allergenic clinical cross-reactivity.57 nsLTPs are also listed as family 14 of the PRs.11

The nsLTPs have a wide distribution, with sequences being available from fruits, nuts, seeds, and vegetables. nsLTPs have been identified as major peach (Pru p 3),58., 59. apple (Mal d 3),60 and apricot (Pru ar 3)61 allergens in Mediterranean populations. The nsLTPs of sweet cherry and the European plum have been reported as the allergens Pru av 362 and Pru d 3,63 respectively. The hazelnut nsLTP, Cor a 8, was described as highly cross-reactive with the peach nsLTP.64 In contrast, the chestnut LTP, Cas s 8, was found to share only certain B cell epitopes with the homologous peach allergen.65 Additional allergenic nsLTPs have been described as Zea m 14 from corn,66 Aspa o 1 from asparagus,67 and Vit v 1 from grape.68 Although allergic reactions to lettuce are not frequent, its nsLTP was reported to cause anaphylaxis in susceptible individuals and has received the designation Lac s 1.69

2.3. The family of cereal α-amylase and protease inhibitors 

Insect pests that feed on plant tissues are responsible for severe crop losses worldwide. Plants have evolved a certain degree of resistance through the production of defense compounds and proteins, including α-amylase inhibitors.70 These inhibitors, which can also possess proteinase inhibitory activity, interfere with the digestion of plant starches and proteins by impeding insect gut enzymes. Inhibitors of this family are produced by wheat, barley, rye, rice, and corn.71 They have subunits of approximately 120 to 160 amino acid residues, contain 4 disulfide bonds (Fig 2, C), and exist as monomers, dimers, or tetramers.

Allergenic members of this family are capable of sensitizing susceptible atopic patients through ingestion or inhalation.72 Allergens within the cereal superfamily of inhibitors include the glycosylated subunits of the tetrameric CM16∗ inhibitor from wheat73; the homologous barley allergens CMb∗,73 Hor v 15 (Hor v 1/BMAI-1),74 and barley dimeric protein75; Sec c 1 from rye flour75; and the rice dimeric α-amylase inhibitors RDAI-1 and RDAI-3.76 The best characterized allergens of this group are the α-amylase inhibitors of rice grain.77., 78.

2.4. Cereal prolamins 

The cereal prolamins, named glutenins and gliadins in wheat, secalins in rye, and hordeins in barley, are the major storage proteins found in the endosperm of cereal grains. The sulfur-rich prolamins are composed of an N-terminal domain that contains proline- and glutamine-rich repeats and a C-terminal nonrepetitive domain with even numbers of cysteine residues that form intrachain disulfide bonds.32 The nonrepetitive domains have been suggested to be rich in α-helices.5 Low-molecular-weight glutenin, α-gliadin, and γ-gliadin have similar repetitive N-terminal domains and nonrepetitive C-terminal domains. In contrast, ω-gliadins consist almost entirely of repeats and are characterized by a low content of sulfur-containing amino acid residues and a lack of cysteine residues.

The highest IgE reactivity was found for low-molecular-weight glutenin, followed by α-gliadin and γ-gliadin.79 ω-5 Gliadin (Tri a 19) was described as an important allergen for young children with immediate allergic reactions to ingested wheat products.80 ω-5 Gliadin from wheat cross-reacts with γ-70 and γ-35 secalins from rye (Sec c 20) and with γ-3 hordein from barley (Hor v 21).81

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3. Proteins of the plant defense system Pathogenesis-related proteins 

The plant defense system makes use of a wide range of compounds and proteins to resist biotic and abiotic stress. PRs are defined as proteins that are induced specifically in a plant as a response to infections by pathogens, such as fungi, bacteria, or viruses, or adverse environmental factors. PRs are not a protein superfamily but represent a collection of unrelated protein families that function as part of the plant defense system. The fact that many plant food allergens are homologous to proteins of the 14 PR families has been extensively reviewed.2., 4., 11., 82., 83.

The PR-3 family includes class I chitinases. Class I chitinases from fruits such as avocado (Pers a 1),84 banana,85 and chestnut (Cas s 5)86 have been identified as major allergens cross-reactive with the latex allergen hevein (Hev b 6.02).87., 88. Allergenic class I chitinases contain a short N-terminal hevein-like domain that shares high sequence identity with latex hevein (Fig 3, A).89 Resistance of a protein to pepsin digestion is a criterion of the Food and Agricultural Organization/World Health Organization decision tree for assessment of the allergenic potential of transgenic foods.90 Although Pers a 1 was extensively degraded when subjected to simulated gastric fluid digestion, the resulting peptides, particularly those corresponding to the hevein-like domain, showed in vitro (ELISA inhibitions) and in vivo (skin prick test) reactivity.91

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  • FIG 3. 

    Stabilization of allergen structures by disulfide bonds. A, Hevein (Hev b 6.02), the major Hevea brasiliensis latex allergen (Protein Data Bank accession no. 1HEV). B, Zeamatin from Zea mays, a member of the PR-5 (TLP) family (1DU5). C, The major kiwifruit allergen actinidin (Act c 1), a papain-like cysteine protease (2ACT). Blue, α-Helices; red, β-strands; yellow, disulfide bonds.

Thaumatin-like proteins (TLPs) are members of the PR-5 family. Mal d 2, an important allergenic TLP of apple fruits, is associated with IgE-mediated symptoms in individuals with apple allergy. Mal d 2 was expressed in Nicotiana benthamiana plants by using a recombinant tobacco mosaic viral vector.92 Purified recombinant Mal d 2 displayed the ability to bind IgE from individuals with apple allergy equivalent to natural Mal d 2. In addition, the recombinant Mal d 2 exhibited antifungal activity, implying a function in plant defense against fungal pathogens. In this context it is interesting to note that zeamatin (Fig 3, B), a TLP from corn, enhanced the efficacy of either nikkomycin Z or clotrimazole in the therapy of Candida-induced vaginitis in a murine model.93 The TLP of sweet cherry, Pru av 2, was identified as a major allergen,94 and the complete coding sequence of Cap a 1, an allergenic TLP of bell pepper, has been published (GenBank/EMBL/DDBJ accession no. AJ297410).95 Recently, a TLP was identified as a minor allergen of grape with an amino acid sequence highly similar to that of Mal d 2 and Pru av 2,68 and a TLP from kiwi was described as the allergen Act c 2.96

Peroxidases are heme-containing enzymes that use H2O2 for a series of oxidative reactions. Specific lignin-forming peroxidases induced by pathogens and involved in plant defense against pathogens have been designated PR-9.97 A peroxidase from wheat flour, also referred to as Tri a Bd 36K, was characterized as a glyoprotein allergen. The carbohydrate moiety seemed to be at least partially involved in IgE binding.98 IgE of patients with food allergy bound to a glycosylated peroxidase from tomato, the cDNA of which coded for 7 potential N-linked gylcosylations sites.99

Individuals with pollen allergy frequently have allergic symptoms after eating certain plant foods. The majority of these reactions are caused by allergens of Rosaceae fruits (eg, apple, apricot, and pear) and Apiaceae vegetables (eg, celery and carrot) that cross-react with allergens that are present in birch pollen, particularly the major birch pollen allergen Bet v 1, and other tree pollen.4., 11., 12. Bet v 1 was the first allergen sequence published that showed homology to PR-10 family members.100 Recently, intriguing data about the biologic activity of Bet v 1 and PR-10 proteins became available. One study provided experimental evidence that Pru av 1, the Bet v 1 homologue from cherry, interacts with phytosteroids, and molecular modeling showed that the hydrophobic cavity of the protein is large enough to accommodate 2 such molecules.101 Mogensen et al102 showed that Bet v 1 had an affinity for a number of ligands, including the plant pigments flavone and naringinin. Markovic-Housley et al103 provided evidence that suggested a plant steroid carrier function for Bet v 1l and other PR-10 proteins by showing the interaction of that Bet v 1 isoform with 2 brassinolide molecules. In a recent study it was shown that Hyp-1, a Bet v 1 homologous protein from St John's wort, was able to catalyze the conversion of emodin to hypericin, a red naphtodianthrone that is effective in the treatment of mild-to-moderate depression.104

Cross-reactivity of Bet v 1 with the major apple allergen Mal d 1 occurs not only at the B-cell but also at the T-cell level.105 Bet v 1 also contains the major T cell–activating region of Api g 1, confirming that Bet v 1 is responsible for initializing an allergic response to the major celery allergen.106 Interestingly, it appears that the epitopes of the hazelnut allergen Cor a 1.04 are less related to the hazel pollen allergen Cor a 1 than to Bet v 1 from birch pollen.107 The Bet v 1–homologous allergen SAM22/Gly m 4 of soybean was found to be responsible for inducing an oral allergy syndrome of extraordinary severity and severe systemic reactions in individuals with birch pollen allergy.108

3.2. Kunitz-type protease inhibitors 

The Kunitz family of soybean trypsin inhibitors is one of the many families of proteinase inhibitors.109 It comprises plant proteins with inhibitory activity against various proteinases, such as serine proteinases from the trypsin and subtilisin families, thiol proteinases, and aspartic proteinases. All members with inhibitory activity contain 2 disulfide bridges. The Kunitz family of trypsin inhibitors is present in a range of legume species and has been characterized in most detail from soybean. The Kunitz soybean trypsin inhibitor has been described as a minor allergen.110 However, the allergen was also reported to induce food anaphylaxis.111 Soy lecithin, which is widely used as an emulsifying agent in processed foods and cosmetic products, contains a small amount of IgE-reactive proteins, the soybean Kunitz inhibitor being one of them.112 IgE-binding potato proteins with molecular weights of 16 to 20 kd were identified as protease inhibitors that belong to the family of Kunitz-type trypsin inhibitors and were designated Sola t 2, 3, and 4.113

3.3. Proteases 

Proteases are grouped into families on the basis of detectable sequence similarity. Two families of proteases contain allergenic proteins, the papain-like cysteine proteases and the subtilisin-like serine proteases. The papain family includes enzymes that are found in many species of eubacteria and eukaryotes.114 Their structures, which are stabilized by 3 conserved disulfide bonds, are composed of 2 domains, one predominantly α-helical and the other containing a β-barrel (Fig 3, C).115 The subtilisin family is the second largest serine protease family, with more than 200 known family members found in archea, bacteria, and eukaryotes.116

The papain family is named after papain from papaya. Similar proteases are found in other fruits, including bromelain from pineapple, actinidin from kiwi, and ficin from fig. Actinidin from kiwi, designated Act c 1, is the major kiwifruit allergen, accounting for 50% of soluble fruit protein and binding IgE from more than 90% of patients with kiwi allergy.117 IgE from patients with kiwi allergy was shown to bind to papain from papaya and bromelain from pineapple.118 P34/Gly m Bd 30K (formerly designated Gly m 1), a major allergen from soybean seed storage vacuoles, shows sequence similarity to papain-like proteases but has lost its enzymatic activity and adopted an alternative function as a syringolide receptor.119 The only allergenic member of the subtilisin family of serine proteases described so far is cucumisin (Cuc m 1) from melon (Cucumis melo), which bound IgE from more than half of the patients with melon allergy studied.120

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4. Profilins 

Profilins are 12- to 15-kd cytosolic proteins that are found in all eukaryotic cells. They bind to monomeric actin and participate in the regulation of polymerization of actin filaments. The major role of profilin in plant cells is the rapid reorganization of microfilaments during processes like cytokinesis, cytoplasmic streaming, cell elongation, and growth of pollen tubes and root hairs.121., 122. Profilin sequences are highly conserved among plants, with 70% to 85% identical residues in sequences of different species. The 2 known allergenic plant profilin structures from birch pollen123 and Hevea brasiliensis latex (Fedorov et al, Protein Data Bank accession number 1G5U) show that the sequence conservation among profilin allergens is reflected by highly similar structures.

Profilin-specific IgE was shown to cross-react between profilins from pollen and food.124., 125. However, the broad spectrum of IgE cross-reactivity usually does not translate into a similarly extensive pattern of clinically overt food allergy.126 Profilins are quite sensitive to heat denaturation and gastric digestion, and thus food allergy caused by profilin is usually confined to the oral allergy syndrome elicited by raw foodstuffs.127., 128. Profilin-specific IgE was detected in 10% to 30% of patients with pollen-related food allergy.14

During recent years, several allergenic profilins from plant food sources were characterized, and their cDNAs were cloned. Allergenic profilins were found in typical birch pollen–related fruits and nuts, such as pear (Pyr c 4), cherry (Pru av 4),129 peach (Pru p 4),130 and hazelnut (Cor a 2).131 Profilins contributing to food allergy among patients with birch and weed pollen allergy include Api g 4 from celery,132 Mus xp 1 from banana,133 and Cuc m 2 from melon.134 The clinical association between grass pollen allergy and oral allergy syndrome to peanut and tomato can be attributed in part to profilin-specific IgE. cDNAs encoding profilins from peanut (Ara h 5),135 tomato (Lyc e 1), and bell pepper (Cap a 2)136 were cloned, and the recombinant proteins were expressed in Escherichia coli. In addition, IgE-binding profilins from soybean (Gly m 3),137 litchi (Lit c 1), and pineapple (Ana c 1)133 were produced as recombinant proteins.

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5. Newly identified classes of allergens 

The number of allergens with known sequences continuously increases. New families of storage and structural proteins and metabolic enzymes are added to the already firmly established protein families that contain allergens. Sola t 1, a patatin storage protein, was described as a novel allergen of potato tuber.138 A peanut oleosin was suggested as a new allergen.139 Oleosins are proteins of 16 to 24 kd that represent the protein components of plant lipid storage bodies called oil bodies.140 Pyr c 5, a Bet v 6–related food allergen from pear, was identified as a phenylcoumaran benzylic ether reductase.141 A minor carrot allergen was identified as a cyclophilin that was not cross-reactive with the homologous birch pollen allergen Bet v 7.142 Lyc e 2, a glycosylated allergen from tomato, was characterized as a β-fructofuranosidase.143 Api g 5, a glycoprotein allergen from celery with homology to flavin adenine dinucleotide-containing oxidases, was used to show that cross-reactive carbohydrates were capable of eliciting allergic reactions in vivo.144

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6. Conclusions 

In addition to the official allergen database of the International Union of Immunological Societies (www.allergen.org) and the Allergome database (www.allergome.org), there are several allergen databases on the Web that are constantly updated.145 These compilations of allergens and information contained in the protein family databases7 have helped shape some of the concepts presented in this article. This system of classifying plant food allergens by protein families provides an important framework for structure-function studies of plant protein allergens. This system also facilitates the prediction of potential allergens. It will be of particular interest to compare the structures of allergenic and nonallergenic members of well-defined protein families to arrive at a clearer understanding of the features of a protein that result in allergenicity.

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Acknowledgments 

Dr Breiteneder thanks Dr Belinda Guerrero-Núñez for fruitful discussions.

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References 

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☆ Series editors: William T. Shearer, MD, PhD, Lanny J. Rosenwasser, MD, and Bruce S. Bochner, MDSupported in part by the Austrian Science Fund Grant SFB018-02.Disclosure of potential conflict of interest: H. Breiteneder—none disclosed. C. Radauer—none disclosed.

PII: S0091-6749(04)00996-0

doi:10.1016/j.jaci.2004.01.779

The Journal of Allergy and Clinical Immunology
Volume 113, Issue 5 , Pages 821-830, May 2004

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