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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한천식알레르기학회(구 대한알레르기학회) Allergy, Asthma & Immunology Research Allergy, Asthma & Immunology Research Vol.11 No.1
- 발행연도
- 2019.1
- 수록면
- 129 - 142 (14page)
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초록· 키워드
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Purpose: Hypoallergenic recombinant Der p 2 has been produced by various genetic manipulations, but mutation of a naturally polymorphic amino acid residue known to affect IgE binding has not been studied. This study aimed to determine the effect of a point mutation (S47W) of residue 47 of Der p 2 on its structure and immunoglobulin (Ig) E binding. Its ability to induce pro-inflammatory responses and to induce blocking IgG antibody was also determined. Methods: S47 of recombinant Der p 2.0110, one of the predominant variants in Bangkok, was mutated to W (S47W). S47W secreted from Pichia pastoris was examined for secondary structure and for the formation of a hydrophobic cavity by 8-Anilino-1-naphthalenesulfonic acid (ANS) staining. Monoclonal and human IgE-antibody binding was determined by enzyme-linked immunosorbent assay. Allergen-induced degranulation by human epsilon receptor expressed-rat basophil was determined. Stimulation of the pro-inflammatory cytokine interleukin (IL)-8 release from human bronchial epithelial (BEAS2B) cells and inhibition of IgE binding to the wild type allergen by S47W-induced IgG were determined. Results: S47W reduced secondary structure and failed to bind the hydrophobic ANS ligand as well as a monoclonal antibody known to be dependent on the nature of the side chain of residue 114 in an adjacent loop. It could also not stimulate IL-8 release from BEAS2B cells. IgE from house dust mite (HDM)-allergic Thais bound S47W with 100-fold weaker avidity, whereas IgE of HDM-allergic Australians did not. S47W still induced basophil degranulation, although requiring higher concentrations for some subjects. Anti-S47W antiserum-immunized mice blocked the binding of human IgE to wild type Der p 2. Conclusions: The mutant S47W had altered structure and reduced ability to stimulate pro-inflammatory responses and to bind IgE, but retained its ability to induce blocking antibodies. It thus represents a hypoallergen produced by a single mutation of a non-solvent-accessible amino acid.
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참고문헌 (25)
참고문헌 신청
Vrtala S / 2014 / Recombinant house dust mite allergens / Methods 66:67~74
Marth K / 2014 / Allergen peptides, recombinant allergens and hypoallergens for allergen-specific immunotherapy / Curr Treat Options Allergy 1:91~106
Derewenda U / 2002 / The crystal structure of a major dust mite allergen Der p 2, and its biological implications / J Mol Biol 318:189~197
Chen KW / 2012 / Hypoallergenic Der p 1/Der p 2 combination vaccines for immunotherapy of house dust mite allergy / J Allergy Clin Immunol 130:435~443
Asturias JA / 2009 / Engineering of major house dust mite allergens Der p 1 and Der p 2 for allergen-specific immunotherapy / Clin Exp Allergy 39:1088~1098
Marth K / 2014 / Allergen peptides, recombinant allergens and hypoallergens for allergen-specific immunotherapy / Curr Treat Options Allergy 1:91~106
Derewenda U / 2002 / The crystal structure of a major dust mite allergen Der p 2, and its biological implications / J Mol Biol 318:189~197
Chen KW / 2012 / Hypoallergenic Der p 1/Der p 2 combination vaccines for immunotherapy of house dust mite allergy / J Allergy Clin Immunol 130:435~443
Asturias JA / 2009 / Engineering of major house dust mite allergens Der p 1 and Der p 2 for allergen-specific immunotherapy / Clin Exp Allergy 39:1088~1098
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