Epitope specificity determines cross-protection of a SIT-induced IgG4 antibody
The calcium-binding 2EF-hand protein Phl p 7 from timothy grass pollen is a highly cross-reactive pollen pan-allergen that can induce severe clinical symptoms in allergic patients. Recently, a human monoclonal Phl p 7-specific IgG4 antibody (mAb102.1F10) was isolated from a patient who had received...
| Autores: | , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Universidad Complutense de Madrid (UCM) |
| Repositorio: | Docta Complutense |
| Idioma: | inglés |
| OAI Identifier: | oai:docta.ucm.es:20.500.14352/24157 |
| Acceso en línea: | https://hdl.handle.net/20.500.14352/24157 |
| Access Level: | acceso abierto |
| Palabra clave: | 577.1 616-056.3 calcium-binding protein cross-reactivity pollen allergen recombinant allergen SIT-induced IgG antibody Alergología Bioquímica (Medicina) 3207.01 Alergias |
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Epitope specificity determines cross-protection of a SIT-induced IgG4 antibodyGadermaier, E.James, L.K.Shamji, M.H.Blatt, K.Fauland, K.Zieglmayer, P.Garmatiuk, T.Focke-Tejkl, M.Villalba Díaz, María TeresaBeavil, R.Keller, W.Valent, P.Durham, S.R.Gould, H.J.Flicker, S.Valenta, R.577.1616-056.3calcium-binding proteincross-reactivitypollen allergenrecombinant allergenSIT-induced IgG antibodyAlergologíaBioquímica (Medicina)3207.01 AlergiasThe calcium-binding 2EF-hand protein Phl p 7 from timothy grass pollen is a highly cross-reactive pollen pan-allergen that can induce severe clinical symptoms in allergic patients. Recently, a human monoclonal Phl p 7-specific IgG4 antibody (mAb102.1F10) was isolated from a patient who had received grass pollen-specific immunotherapy (SIT).We studied epitope specificity, cross-reactivity, affinity and cross-protection of mAb102.1F10 towards homologous calcium-binding pollen allergens. Sequence comparisons and molecular modelling studies were performed with ClustalW and SPADE, respectively. Surface plasmon resonance measurements were done with purified recombinant allergens. Binding and cross-reactivity of patients’ IgE and mAb102.1F10 to calcium-binding allergens and peptides thereof was studied with quantitative RAST-based methods, in ELISA, basophil activation and IgE-facilitated allergen presentation experiments. Allergens from Timothy grass (Phl p 7), Alder (Aln g 4), Birch (Bet v 4), Turnip rape (Bra r 1), Lamb′s quarter (Che a 3) and Olive (Ole e 3, Ole e 8) showed high sequence similarity and cross-reacted with allergic patients’ IgE. mAb102.1F10 bound the C-terminal portion of Phl p 7 in a calcium-dependent manner. It cross-reacted with high affinity with Ole e 3 whereas binding and affinity to the other allergens was low. mAb102.1F10 showed limited inhibition of patients’ IgE binding and basophil activation. Sequence comparison and surface exposure calculations identified three amino acids likely to be responsible for limited cross-reactivity.Our results demonstrate that a small number of amino acid differences among cross-reactive allergens can reduce the affinity of binding by a SIT-induced IgG and thus limit cross-protection.WileyUniversidad Complutense de Madrid20152015-09-3020152015-09-30journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/24157reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/241572026-06-02T12:44:21Z |
| dc.title.none.fl_str_mv |
Epitope specificity determines cross-protection of a SIT-induced IgG4 antibody |
| title |
Epitope specificity determines cross-protection of a SIT-induced IgG4 antibody |
| spellingShingle |
Epitope specificity determines cross-protection of a SIT-induced IgG4 antibody Gadermaier, E. 577.1 616-056.3 calcium-binding protein cross-reactivity pollen allergen recombinant allergen SIT-induced IgG antibody Alergología Bioquímica (Medicina) 3207.01 Alergias |
| title_short |
Epitope specificity determines cross-protection of a SIT-induced IgG4 antibody |
| title_full |
Epitope specificity determines cross-protection of a SIT-induced IgG4 antibody |
| title_fullStr |
Epitope specificity determines cross-protection of a SIT-induced IgG4 antibody |
| title_full_unstemmed |
Epitope specificity determines cross-protection of a SIT-induced IgG4 antibody |
| title_sort |
Epitope specificity determines cross-protection of a SIT-induced IgG4 antibody |
| dc.creator.none.fl_str_mv |
Gadermaier, E. James, L.K. Shamji, M.H. Blatt, K. Fauland, K. Zieglmayer, P. Garmatiuk, T. Focke-Tejkl, M. Villalba Díaz, María Teresa Beavil, R. Keller, W. Valent, P. Durham, S.R. Gould, H.J. Flicker, S. Valenta, R. |
| author |
Gadermaier, E. |
| author_facet |
Gadermaier, E. James, L.K. Shamji, M.H. Blatt, K. Fauland, K. Zieglmayer, P. Garmatiuk, T. Focke-Tejkl, M. Villalba Díaz, María Teresa Beavil, R. Keller, W. Valent, P. Durham, S.R. Gould, H.J. Flicker, S. Valenta, R. |
| author_role |
author |
| author2 |
James, L.K. Shamji, M.H. Blatt, K. Fauland, K. Zieglmayer, P. Garmatiuk, T. Focke-Tejkl, M. Villalba Díaz, María Teresa Beavil, R. Keller, W. Valent, P. Durham, S.R. Gould, H.J. Flicker, S. Valenta, R. |
| author2_role |
author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universidad Complutense de Madrid |
| dc.subject.none.fl_str_mv |
577.1 616-056.3 calcium-binding protein cross-reactivity pollen allergen recombinant allergen SIT-induced IgG antibody Alergología Bioquímica (Medicina) 3207.01 Alergias |
| topic |
577.1 616-056.3 calcium-binding protein cross-reactivity pollen allergen recombinant allergen SIT-induced IgG antibody Alergología Bioquímica (Medicina) 3207.01 Alergias |
| description |
The calcium-binding 2EF-hand protein Phl p 7 from timothy grass pollen is a highly cross-reactive pollen pan-allergen that can induce severe clinical symptoms in allergic patients. Recently, a human monoclonal Phl p 7-specific IgG4 antibody (mAb102.1F10) was isolated from a patient who had received grass pollen-specific immunotherapy (SIT).We studied epitope specificity, cross-reactivity, affinity and cross-protection of mAb102.1F10 towards homologous calcium-binding pollen allergens. Sequence comparisons and molecular modelling studies were performed with ClustalW and SPADE, respectively. Surface plasmon resonance measurements were done with purified recombinant allergens. Binding and cross-reactivity of patients’ IgE and mAb102.1F10 to calcium-binding allergens and peptides thereof was studied with quantitative RAST-based methods, in ELISA, basophil activation and IgE-facilitated allergen presentation experiments. Allergens from Timothy grass (Phl p 7), Alder (Aln g 4), Birch (Bet v 4), Turnip rape (Bra r 1), Lamb′s quarter (Che a 3) and Olive (Ole e 3, Ole e 8) showed high sequence similarity and cross-reacted with allergic patients’ IgE. mAb102.1F10 bound the C-terminal portion of Phl p 7 in a calcium-dependent manner. It cross-reacted with high affinity with Ole e 3 whereas binding and affinity to the other allergens was low. mAb102.1F10 showed limited inhibition of patients’ IgE binding and basophil activation. Sequence comparison and surface exposure calculations identified three amino acids likely to be responsible for limited cross-reactivity.Our results demonstrate that a small number of amino acid differences among cross-reactive allergens can reduce the affinity of binding by a SIT-induced IgG and thus limit cross-protection. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2015 2015-09-30 2015 2015-09-30 |
| dc.type.none.fl_str_mv |
journal article http://purl.org/coar/resource_type/c_6501 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/20.500.14352/24157 |
| url |
https://hdl.handle.net/20.500.14352/24157 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Atribución 3.0 España https://creativecommons.org/licenses/by/3.0/es/ |
| dc.rights.openaire.fl_str_mv |
info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Atribución 3.0 España https://creativecommons.org/licenses/by/3.0/es/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Wiley |
| publisher.none.fl_str_mv |
Wiley |
| dc.source.none.fl_str_mv |
reponame:Docta Complutense instname:Universidad Complutense de Madrid (UCM) |
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Universidad Complutense de Madrid (UCM) |
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Docta Complutense |
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Docta Complutense |
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