Hypoallergenic mutants of the major oyster allergen Cra g 1 alleviate oyster tropomyosin allergenic potency
Copyright © 2020 Elsevier B.V. All rights reserved..
Design of hypoallergen with low IgE reactivity is desirable for allergen-specific immunotherapy. Despite oyster tropomyosin (Cra g 1) is considered as the major allergen, no immunotherapy is available now. In the current research, we generated hypoallergens of Cra g 1 and evaluated their allergenicity. Four hypoallergenic derivatives were constructed by epitope deletion or site-directed mutagenesis on grounds of the identified epitopes. They showed obvious reduction in reactivity towards IgE from oyster-allergic patients and Cra g 1-sensitized BN rats, as well as significant decrease in degranulation and secretion of allergic mediators including histamine, IL-4, IL-6 and TNF-α. In addition, to further investigate the molecular mechanism, we examined the effects of these variants on FcεRI-dependent signalling pathway in IgE-challenged RBL-2H3 cells. We found that the hypoallergenic mutants were able to attenuate FcεRI-mediated signaling cascades in tested cells. These results indicate that the hypoallergenic molecules have ideal characteristics and offer a promising new strategy in clinical immunotherapy for shellfish-allergic subjects.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:164 |
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| Enthalten in: |
International journal of biological macromolecules - 164(2020) vom: 01. Dez., Seite 1973-1983 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Jiangtao [VerfasserIn] |
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| Links: |
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| Themen: |
37341-29-0 |
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| Anmerkungen: |
Date Completed 06.04.2021 Date Revised 06.04.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijbiomac.2020.07.325 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM313337446 |
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| 245 | 1 | 0 | |a Hypoallergenic mutants of the major oyster allergen Cra g 1 alleviate oyster tropomyosin allergenic potency |
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| 500 | |a Date Revised 06.04.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 Elsevier B.V. All rights reserved. | ||
| 520 | |a Design of hypoallergen with low IgE reactivity is desirable for allergen-specific immunotherapy. Despite oyster tropomyosin (Cra g 1) is considered as the major allergen, no immunotherapy is available now. In the current research, we generated hypoallergens of Cra g 1 and evaluated their allergenicity. Four hypoallergenic derivatives were constructed by epitope deletion or site-directed mutagenesis on grounds of the identified epitopes. They showed obvious reduction in reactivity towards IgE from oyster-allergic patients and Cra g 1-sensitized BN rats, as well as significant decrease in degranulation and secretion of allergic mediators including histamine, IL-4, IL-6 and TNF-α. In addition, to further investigate the molecular mechanism, we examined the effects of these variants on FcεRI-dependent signalling pathway in IgE-challenged RBL-2H3 cells. We found that the hypoallergenic mutants were able to attenuate FcεRI-mediated signaling cascades in tested cells. These results indicate that the hypoallergenic molecules have ideal characteristics and offer a promising new strategy in clinical immunotherapy for shellfish-allergic subjects | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cra g 1 | |
| 650 | 4 | |a Hypoallergen | |
| 650 | 4 | |a IgE | |
| 650 | 4 | |a Mediator | |
| 650 | 4 | |a RBL-2H3 cells | |
| 650 | 7 | |a Allergens |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 650 | 7 | |a Tropomyosin |2 NLM | |
| 650 | 7 | |a Immunoglobulin E |2 NLM | |
| 650 | 7 | |a 37341-29-0 |2 NLM | |
| 700 | 1 | |a Liu, Wenying |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ruixue |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xiaohan |e verfasserin |4 aut | |
| 700 | 1 | |a Fang, Lei |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Xiuyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Ruizeng |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Guoming |e verfasserin |4 aut | |
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