Background: It is not known why some foods sensitizing via the gastrointestinal tract are prevalent allergenic foods and others are not. Eating habits, processing, and the food matrix have been suggested to influence the allergenicity of a given food. Factors related to protein structure, such as stability to digestion, have also been suggested. 7S globulins from peanut, hazelnut, soy, and pea were studied to determine whether related proteins would induce a similar sensitization when removed from their ‘normal’ matrix. Methods: Brown Norway rats (soy tolerant or nontolerant) were immunized i.p. 3 times with 100 µg purified peanut, hazelnut, soy, or pea 7S without adjuvant. Sera were analyzed for specific antibodies by different ELISAs (IgG1, IgG2a, and IgE), inhibition ELISA, and rat basophilic leukemia cell assay. Results: The 4 related 7S globulins induced a response with an almost identical level of specific antibodies, but peanut 7S induced IgE of higher avidity than hazelnut and pea 7S which, again, had a higher avidity than IgE induced by soy 7S. Soy tolerance reduced the functionality of IgE without influencing antibody titers. Conclusions: Although the 4 7S globulins are structurally related allergens, they induce antibodies with different antigen-binding characteristics. Peanut 7S induces IgE of a higher avidity than hazelnut and pea 7S which, again, has a higher avidity than IgE induced by soy 7S. We also show that soy tolerance influences the function of antibodies to peanut 7S. These findings may help explain how antibodies of different clinical significances can develop in different individuals sensitized to the same allergen.

1.
Breiteneder H, Mills EN: Molecular properties of food allergens. J Allergy Clin Immunol 2005;115:14–23.
2.
Mills EN, Jenkins JA, Alcocer MJ, Shewry PR: Structural, biological, and evolutionary relationships of plant food allergens sensitizing via the gastrointestinal tract. Crit Rev Food Sci Nutr 2004;44:379–407.
3.
Jenkins JA, Griffiths-Jones S, Shewry PR, Breiteneder H, Mills EN: Structural relatedness of plant food allergens with specific references to cross-reactive allergens: an in silico analysis. J Allergy Clin Immunol 2005;115:163–170.
4.
Mills EN, Jenkins JA, Bannon GA: Plant seed globulin allergens; in Mills EN, Shewry PR (eds): Plant Food Allergens. Oxford, Blackwell Science, 2004, pp 141–157.
5.
Mills EN, Jenkins JA, Marigheto N, Belton PS, Gunning AP, Morris VJ: Allergens of the cupin superfamily. Biochem Soc Trans 2002;30:925–929.
6.
Murzin AG, Brenner SE, Hubbard T, Chothia C: SCOP: a structural classification of proteins database for the investigation of sequences and structures. J Mol Biol 1995;247:536–540.
7.
Breiteneder H, Radauer CA: A classification of plant food allergens. J Allergy Clin Immunol 2004;113:821–830.
8.
Ferreira F, Hirtenlehner K, Jilek A, Godnik-Cvar J, Breiteneder H, Grimm R, Hoffmann-Sommergruber K, Scheiner O, Kraft D, Breitenbach M, Rheinberger HJ, Ebner C: Dissection of immunoglobulin E and T lymphocyte reactivity of isoforms of the major birch pollen allergen Bet v 1: potential use of hypoallergenic isoforms for immunotherapy. J Exp Med 1996;183:599–609.
9.
Aalberse RC: Structural biology of allergens. J Allergy Clin Immunol 2000;106:228–238.
10.
Bernhisel-Broadbent J, Sampson H: Cross-allergenicity in the legume botanical family in children with food hypersensitivity. J Allergy Clin Immunol 1989;83:435–440.
11.
Bernhisel-Broadbent J, Taylor S, Sampson H: Cross-allergenicity in the legume botanical family in children with food hypersensitivity. 2. Laboratory correlates. J Allergy Clin Immunol 1989;84:701–709.
12.
Rona RJ, Keil T, Summers C, Gislason D, Zuidmeer L, Sodergren E, Sigurdardottir ST, Lindner T, Goldhahn K, Dahlstrom J, McBride D, Madsen C: The prevalence of food allergy: a meta-analysis. J Allergy Clin Immunol 2007;120:638–646.
13.
Zuidmeer L, Goldhahn K, Rona RJ, Gislason D, Madsen C, Summers C, Sodergren E, Dahlstrom J, Lindner T, Sigurdardottir ST, McBride D, Keil T: The prevalence of plant food allergies: a systematic review. J Allergy Clin Immunol 2008;121:1210–1218.
14.
Grundy J, Matthews S, Bateman B, Dean T, Arshed SH: Rising prevalence of allergy to peanut in children: data from 2 sequential cohorts. J Allergy Clin Immunol 2002;110:784–789.
15.
Burks AW, Williams LW, Helm RM, Connaughton C, Cockrell G, O’Brien T: Identification of a major allergen, Ara h 1, in patients with atopic dermatitis and positive peanut challenges. J Allergy Clin Immunol 1991;88:172–179.
16.
Bøgh KL, Kroghsbo S, Dahl L, Rigby NM, Barkholt V, Mills EN, Madsen CB: Digested Ara h 1 has sensitizing capacity in Brown Norway rats. Clin Exp Allergy 2009;39:1611–1621.
17.
Eiwegger T, Rigby N, Mondoulet L, Bernard H, Krauth MT, Boehm A, Dehlink E, Valent P, Wal JM, Mills EN, Szépfalusi Z: Gastro-duodenal digestion products of the major peanut allergen Ara h 1 retain an allergenic potential. Clin Exp Allergy 2006;36:1281–1288.
18.
Lauer I, Foetisch, Kolarich D, Ballmer-Weber BK, Conti A, Altmann F, Vieths S, Scheurer S: Hazelnut (Corylus avellana) vicilin Cor a 11: molecular characterization of a glycoprotein and its allergenic activity. Biochem J 2004;383:327–334.
19.
Holzhauser T, Wackermann O, Ballmer-Weber BK, Bindslev-Jensen C, Scibilia J, Perono-Garoffo L, Utsumi S, Poulsen LK, Vieths S: Soybean (Glycine max) allergy in Europe: Gly m 5 (beta-conglycinin) and Gly m 6 (glycinin) are potential diagnostic markers for severe allergic reactions to soy. J Allergy Clin Immunol 2009;123:452–458.
20.
Sanchez-Monge R, Lopez-Torrejón G, Pascual CY, Varela J, Martin-Esteban M, Salcedo G: Vicilin and convicilin are potential major allergens from pea. Clin Exp Allergy 2004;34:1747–1753.
21.
Holt PG, Turner KJ: Persistent IgE-secreting cells which are refractory to T-cell control. Int Arch Allergy Appl Immunol 1985;77:45–46.
22.
Knippels LM, Penninks AH, van Meeteren M, Houben GF: Humoral and cellular immune responses in different rat strains on oral exposure to ovalbumin. Food Chem Toxicol 1999;37:881–888.
23.
Knippels LM, Penninks AH: Recent advances using rodent models for predicting human allergenicity. Toxicol Appl Pharmacol 2005;207:S157–S160.
24.
Dearman RJ, Kimber I: A mouse model for food allergy using intraperitoneal sensitization. Methods 2007;41:91–98.
25.
Barkholt V, Jensen AL: Amino acid analysis: determination of cysteine plus half-cysteine in proteins after hydrochloric acid hydrolysis with a disulfide compound as additive. Anal Biochem 1989;177:318–322.
26.
Marsh J, Rigby N, Wellner K, Reese G, Knulst A, Akkerdaas J, van Ree R, Radauer C, Lovegrove A, Sancho A, Mills C, Vieths S, Hoffmann-Sommergruber K, Shewry PR: Purification and characterisation of a panel of peanut allergens suitable for use in allergy diagnosis. Mol Nutr Food Res 2008;52:S272–S285.
27.
Rigby NM, Marsh J, Sancho AI, Wellner K, Akkerdaas J, van Ree R, Knulst A, Fernández-Rivas M, Brettlova V, Schilte PP, Summer C, Pumphrey R, Shewry PR, Mills EN: The purification and characterisation of allergenic hazelnut seed proteins. Mol Nutr Food Res 2008;52:S251–S261.
28.
Brix S, Kjaer TM, Barkholt V, Frøkiaer H: Lipopolysaccharide contamination of beta-lactoglobulin affects the immune response against intraperitoneally and orally administered antigen. Int Arch Allergy Immunol 2004;135:216–220.
29.
Nagano T, Hirotsuka M, Mori H, Kohyama K, Nishinari K: Dynamic viscoelastic study on the gelation of 7S globulin from soybeans. J Agric Food Chem 1992;40:941–944.
30.
Huang L, Mills EN, Carter JM, Morgan MR: Analysis of thermal stability of soya globulins using monoclonal antibodies. Biochim Biophys Acta 1998;1388:215–226.
31.
Boulter D: Cloning of pea storage protein genes. Philos Trans R Soc Lond B Biol Sci 1984;304:323–332.
32.
Suchkov VV, Popello IA, Grinberg VY, Tolstoguzov VB: Isolation and purification of 7S and 11S globulins from broad beans and peas. J Agric Food Chem 1990;38:92–95.
33.
Hoffmann-Sommergruber K, Mills EN, Vieths S: Coordinated and standardized production, purification and characterization of natural and recombinant food allergens to establish a food allergen library. Mol Nutr Food Res 2008;52:S159–S165.
34.
Pappin DJ, Hojrup P, Bleasby AJ: Rapid identification of proteins by peptide-mass fingerprinting. Curr Biol 1993;3:327–332.
35.
Reeves PG, Nielsen FH, Fahey GC Jr: AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr 1993;123:1939–1951.
36.
Kroghsbo S, Madsen C, Poulsen M, Schrøder M, Kvist PH, Taylor M, Gatehouse A, Shu Q, Knudsen I: Immunotoxicological studies of genetically modified rice expressing PHA-E lectin or Bt toxin in Wistar rats. Toxicology 2008;245:24–34.
37.
Christensen HR, Brix S, Frøkiaer H: Immune response in mice to ingested soya protein: antibody production, oral tolerance and maternal transfer. Br J Nutr 2004;91:725–732.
38.
Brix S, Christensen HR, Barkholt V, Frøkiaer H: Effect of maternal dietary cow’s milk on the immune response to beta-lactoglobulin in the offspring: a four-generation study in mice. Int Arch Allergy Immunol 2005;136:250–257.
39.
de Jonge JD, Knippels LM, Ezendam J, Odink J, Penninks AH, van Loveren H: The importance of dietary control in the development of a peanut allergy model in Brown Norway rats. Methods 2007;41:99–111.
40.
Repa A, Kozakova H, Hudcovic T, Stepankova R, Hrncir T, Tlaskalova-Hogenova H, Pollak A, Wiedermann U: Susceptibility to nasal and oral tolerance induction to the major birch pollen allergen Bet v 1 is not dependent on the presence of the microflora. Immunol Lett 2008;117:50–56.
41.
Kjaer TM, Frøkiaer H: Induction of oral tolerance with micro-doses of ovomucoid depends on the length of the feeding period. Scand J Immunol 2002;55:359–365.
42.
Horner AA: Defining a role for mucosal immunity in the prevention and pathogenesis of respiratory allergic diseases. Curr Immunol Rev 2006;2:157–167.
43.
van Wijk F, Knippels L: Initiating mechanisms of food allergy: oral tolerance versus allergic sensitization. Biomed Pharmacother 2007;61:8–20.
44.
Aviszus K, Zhang X, Wysocki LJ: Silent development of memory progenitor B cells. J Immunol 2007;179:5181–5190.
45.
Fish S, Zenowich E, Fleming M, Manser T: Molecular analysis of original antigenic sin. 1. clonal selection, somatic mutation, and isotype switching during a memory B cell response. J Exp Med 1989;170:1191–1209.
46.
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;113:776–782.
47.
El-Khouly F, Lewis SA, Pons L, Burks AW, Hourihane JO: IgG and IgE avidity characteristics of peanut allergic individuals. Pediatr Allergy Immunol 2007;18:607–613.
48.
Mita H, Yasueda H, Akiyama K: Affinity of IgE antibody to antigen influences allergen-induced histamine release. Clin Exp Allergy 2000;30:1583–1589.
49.
Christensen LH, Holm J, Lund G, Riise E, Lund K: Several distinct properties of the IgE repertoire determine effector cell degranulation in response to allergen challenge. J Allergy Clin Immunol 2008;122:298–304.
50.
Saalman R, Dahlgren UI, Fällström SP, Hanson LA, Ahlstedt S, Wold AE: Avidity progression of dietary antibodies in healthy and coeliac children. Clin Exp Immunol 2003;134:328–334.
51.
Scheurer S, Son DY, Boehm M, Karamloo F, Franke S, Hoffmann A, Haustein D, Vieths S: Cross-reactivity and epitope analysis of Pru a 1, the major cherry allergen. Mol Immunol 1999;36:155–167.
52.
Wagner S, Radauer C, Bublin M, Hoffmann-Sommergruber K, Kopp T, Greisenegger EK, Vogel L, Vieths S, Scheiner O: Naturally occurring hypoallergenic Bet v 1 isoforms fail to induce IgE responses in individuals with birch pollen allergy. J Allergy Clin Immunol 2008;121:246–252.
53.
Hsu SC, Tsai TH, Kawasaki H, Chen CH, Plunkett B, Lee RT, Lee YC, Huang SK: Antigen coupled with Lewis-x trisaccharides elicits potent immune responses in mice. J Allergy Clin Immunol 2007;119:1522–1528.
54.
Wills-Karp M, Nathan A, Page K, Karp CL: New insights into innate immune mechanisms underlying allergenicity. Mucosal Immunol 2010;3:104–110.
55.
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;177:3677–3685.
56.
Maruyama N, Adachi M, Takahashi K, Yagasaki K, Kohno M, Takenaka Y, Okuda E, Nakagawa S, Mikami B, Utsumi S: Crystal structures of recombinant and native soybean beta-conglycinin beta homotrimers. Eur J Biochem 2001;268:3595–3604.
57.
Asero R, Ballmer-Weber BK, Beyer K, Conti A, Dubakiene R, Fernandez-Rivas M, Hoffmann-Sommergruber K, Lidholm J, Mustakov T, Oude Elberink JN, Pumphrey RS, Stahl Skov P, van Ree R, Vlieg-Boerstra BJ, Hiller R, Hourihane JO, Kowalski M, Papadopoulos NG, Wal JM, Mills EN, Vieths S: IgE-mediated food allergy diagnosis: current status and new perspectives. Mol Nutr Food Res 2007;51:135–147.
58.
Hoffmann-Sommergruber K, Mills EN: Food allergen protein families and their structural characteristics and application in component-resolved diagnosis: new data from the EuroPrevall project. Anal Bioanal Chem 2009;395:25–35.
59.
Kroghsbo S, Rigby N, Mackie A, Mills C, Salt L, Bøgh K, Madsen C: Food processing affects the immunogenic and allergenic potential of peanut and soy allergens in an oral rat model. Allergy 2009;64:S373–S374.
60.
Mine Y, Yang M: Epitope characterization of ovalbumin in BALB/c mice using different entry routes. Biochim Biophys Acta 2007;1774:200–212.
61.
Pons L, Ponnappan U, Hall RA, Simpson P, Cockrell G, West CM, Sampson HA, Helm RM, Burks AW: Soy immunotherapy for peanut-allergic mice: modulation of the peanut-allergic response. J Allergy Clin Immunol 2004;114:915–921.
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