Targeting a cross-reactive Gly m 5 soy peptide as responsible for hypersensitivity reactions in a milk allergy mouse model.

<h4>Background</h4>Cross-reactivity between soybean allergens and bovine caseins has been previously reported. In this study we aimed to map epitopes of the major soybean allergen Gly m 5 that are co-recognized by casein specific antibodies, and to identify a peptide responsible for the...

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Autores principales: Renata Curciarello, Paola L Smaldini, Angela M Candreva, Virginia González, Gustavo Parisi, Ana Cauerhff, Ivana Barrios, Luis Bruno Blanch, Carlos A Fossati, Silvana Petruccelli, Guillermo H Docena
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Publicado: Public Library of Science (PLoS) 2014
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Acceso en línea:https://doaj.org/article/a83a2dfff6c247a4af42501402817902
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spelling oai:doaj.org-article:a83a2dfff6c247a4af425014028179022021-11-18T08:38:16ZTargeting a cross-reactive Gly m 5 soy peptide as responsible for hypersensitivity reactions in a milk allergy mouse model.1932-620310.1371/journal.pone.0082341https://doaj.org/article/a83a2dfff6c247a4af425014028179022014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24416141/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Cross-reactivity between soybean allergens and bovine caseins has been previously reported. In this study we aimed to map epitopes of the major soybean allergen Gly m 5 that are co-recognized by casein specific antibodies, and to identify a peptide responsible for the cross-reactivity.<h4>Methods</h4>Cow's milk protein (CMP)-specific antibodies were used in different immunoassays (immunoblotting, ELISA, ELISA inhibition test) to evaluate the in vitro recognition of soybean proteins (SP). Recombinant Gly m 5 (α), a truncated fragment containing the C-terminal domain (α-T) and peptides of α-T were obtained and epitope mapping was performed with an overlapping peptide assay. Bioinformatics tools were used for epitope prediction by sequence alignment, and for modelling the cross-recognized soy proteins and peptides. The binding of SP to a monoclonal antibody was studied by surface Plasmon resonance (SPR). Finally, the in vivo cross-recognition of SP was assessed in a mouse model of milk allergy.<h4>Results</h4>Both α and α-T reacted with the different CMP-specific antibodies. α-T contains IgG and IgE epitopes in several peptides, particularly in the peptide named PA. Besides, we found similar values of association and dissociation constants between the α-casein specific mAb and the different milk and soy components. The food allergy mouse model showed that SP and PA contain the cross-reactive B and T epitopes, which triggered hypersensitivity reactions and a Th2-mediated response on CMP-sensitized mice.<h4>Conclusions</h4>Gly m 5 is a cross-reactive soy allergen and the α-T portion of the molecule contains IgG and IgE immunodominant epitopes, confined to PA, a region with enough conformation to be bound by antibodies. These findings contribute to explain the intolerance to SP observed in IgE-mediated CMA patients, primarily not sensitised to SP, as well as it sets the basis to propose a mucosal immunotherapy for milk allergy using this soy peptide.Renata CurciarelloPaola L SmaldiniAngela M CandrevaVirginia GonzálezGustavo ParisiAna CauerhffIvana BarriosLuis Bruno BlanchCarlos A FossatiSilvana PetruccelliGuillermo H DocenaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e82341 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Renata Curciarello
Paola L Smaldini
Angela M Candreva
Virginia González
Gustavo Parisi
Ana Cauerhff
Ivana Barrios
Luis Bruno Blanch
Carlos A Fossati
Silvana Petruccelli
Guillermo H Docena
Targeting a cross-reactive Gly m 5 soy peptide as responsible for hypersensitivity reactions in a milk allergy mouse model.
description <h4>Background</h4>Cross-reactivity between soybean allergens and bovine caseins has been previously reported. In this study we aimed to map epitopes of the major soybean allergen Gly m 5 that are co-recognized by casein specific antibodies, and to identify a peptide responsible for the cross-reactivity.<h4>Methods</h4>Cow's milk protein (CMP)-specific antibodies were used in different immunoassays (immunoblotting, ELISA, ELISA inhibition test) to evaluate the in vitro recognition of soybean proteins (SP). Recombinant Gly m 5 (α), a truncated fragment containing the C-terminal domain (α-T) and peptides of α-T were obtained and epitope mapping was performed with an overlapping peptide assay. Bioinformatics tools were used for epitope prediction by sequence alignment, and for modelling the cross-recognized soy proteins and peptides. The binding of SP to a monoclonal antibody was studied by surface Plasmon resonance (SPR). Finally, the in vivo cross-recognition of SP was assessed in a mouse model of milk allergy.<h4>Results</h4>Both α and α-T reacted with the different CMP-specific antibodies. α-T contains IgG and IgE epitopes in several peptides, particularly in the peptide named PA. Besides, we found similar values of association and dissociation constants between the α-casein specific mAb and the different milk and soy components. The food allergy mouse model showed that SP and PA contain the cross-reactive B and T epitopes, which triggered hypersensitivity reactions and a Th2-mediated response on CMP-sensitized mice.<h4>Conclusions</h4>Gly m 5 is a cross-reactive soy allergen and the α-T portion of the molecule contains IgG and IgE immunodominant epitopes, confined to PA, a region with enough conformation to be bound by antibodies. These findings contribute to explain the intolerance to SP observed in IgE-mediated CMA patients, primarily not sensitised to SP, as well as it sets the basis to propose a mucosal immunotherapy for milk allergy using this soy peptide.
format article
author Renata Curciarello
Paola L Smaldini
Angela M Candreva
Virginia González
Gustavo Parisi
Ana Cauerhff
Ivana Barrios
Luis Bruno Blanch
Carlos A Fossati
Silvana Petruccelli
Guillermo H Docena
author_facet Renata Curciarello
Paola L Smaldini
Angela M Candreva
Virginia González
Gustavo Parisi
Ana Cauerhff
Ivana Barrios
Luis Bruno Blanch
Carlos A Fossati
Silvana Petruccelli
Guillermo H Docena
author_sort Renata Curciarello
title Targeting a cross-reactive Gly m 5 soy peptide as responsible for hypersensitivity reactions in a milk allergy mouse model.
title_short Targeting a cross-reactive Gly m 5 soy peptide as responsible for hypersensitivity reactions in a milk allergy mouse model.
title_full Targeting a cross-reactive Gly m 5 soy peptide as responsible for hypersensitivity reactions in a milk allergy mouse model.
title_fullStr Targeting a cross-reactive Gly m 5 soy peptide as responsible for hypersensitivity reactions in a milk allergy mouse model.
title_full_unstemmed Targeting a cross-reactive Gly m 5 soy peptide as responsible for hypersensitivity reactions in a milk allergy mouse model.
title_sort targeting a cross-reactive gly m 5 soy peptide as responsible for hypersensitivity reactions in a milk allergy mouse model.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/a83a2dfff6c247a4af42501402817902
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