IgE Epitopes of the House Dust Mite Allergen Der p 7 Are Mainly Discontinuous and Conformational.
Allergens
/ chemistry
Animals
Antigens, Dermatophagoides
/ chemistry
Arthropod Proteins
/ chemistry
Case-Control Studies
Cell Line, Tumor
Epitope Mapping
Humans
Immunodominant Epitopes
Immunoglobulin E
/ blood
Models, Molecular
Protein Conformation
Protein Folding
Pyroglyphidae
/ genetics
Rabbits
Rats
Respiratory Hypersensitivity
/ blood
Der p 7
IgE epitope mapping
allergen
allergen structure
allergy
house dust mite allergy
peptides
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
29
03
2021
accepted:
30
04
2021
entrez:
5
7
2021
pubmed:
6
7
2021
medline:
29
10
2021
Statut:
epublish
Résumé
Several studies indicate that Der p 7 is an important and clinically relevant allergen of Recombinant Der p 7 was expressed and purified, analyzed for fold by circular dichroism and tested for its allergenic activity by basophil activation. Seven overlapping, surface-exposed peptides (P1-P7) with a length of 27 to 37 amino acids, which spanned the Der p 7 sequence, were synthesized and tested for IgE reactivity and allergenic activity by basophil activation assay. Carrier-bound peptides were studied for their ability to induce allergen-specific IgG antibodies in rabbits. Peptide-specific antibodies were used to inhibit allergic patients` IgE binding to Der p 7 by ELISA for mapping of IgE epitopes. rDer p 7 showed high allergenic activity comparable with Der p 5, Der p 21, and Der p 23. None of the seven tested peptides showed any IgE reactivity or allergenic activity when tested with HDM- allergic patients indicating lack of sequential IgE epitopes on Der p 7. IgE inhibition experiments using anti-peptide specific IgGs and molecular modeling enabled us to identify discontinuous, conformational IgE epitopes of Der p 7. IgE epitopes of Der p 7 belong to the conformational and discontinuous type whereas sequential Der p 7 peptides lack IgE reactivity. It should thus be possible to construct hypoallergenic vaccines for Der p 7 based on carrier-bound allergen peptides.
Sections du résumé
Background
Several studies indicate that Der p 7 is an important and clinically relevant allergen of
Methods
Recombinant Der p 7 was expressed and purified, analyzed for fold by circular dichroism and tested for its allergenic activity by basophil activation. Seven overlapping, surface-exposed peptides (P1-P7) with a length of 27 to 37 amino acids, which spanned the Der p 7 sequence, were synthesized and tested for IgE reactivity and allergenic activity by basophil activation assay. Carrier-bound peptides were studied for their ability to induce allergen-specific IgG antibodies in rabbits. Peptide-specific antibodies were used to inhibit allergic patients` IgE binding to Der p 7 by ELISA for mapping of IgE epitopes.
Results
rDer p 7 showed high allergenic activity comparable with Der p 5, Der p 21, and Der p 23. None of the seven tested peptides showed any IgE reactivity or allergenic activity when tested with HDM- allergic patients indicating lack of sequential IgE epitopes on Der p 7. IgE inhibition experiments using anti-peptide specific IgGs and molecular modeling enabled us to identify discontinuous, conformational IgE epitopes of Der p 7.
Conclusion and Clinical Relevance
IgE epitopes of Der p 7 belong to the conformational and discontinuous type whereas sequential Der p 7 peptides lack IgE reactivity. It should thus be possible to construct hypoallergenic vaccines for Der p 7 based on carrier-bound allergen peptides.
Identifiants
pubmed: 34220841
doi: 10.3389/fimmu.2021.687294
pmc: PMC8241568
doi:
Substances chimiques
Allergens
0
Antigens, Dermatophagoides
0
Arthropod Proteins
0
Dermatophagoides pteronyssinus antigen p 7
0
Immunodominant Epitopes
0
Immunoglobulin E
37341-29-0
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
687294Informations de copyright
Copyright © 2021 Curin, Huang, Garmatiuk, Gutfreund, Resch-Marat, Chen, Fauland, Keller, Zieglmayer, Zieglmayer, Lemell, Horak, Hemmer, Focke-Tejkl, Flicker, Vrtala and Valenta.
Déclaration de conflit d'intérêts
RV has received research grants from Viravaxx, Vienna, Austria, HVD Biotech, Vienna, Austria and WORG Pharmaceuticals, Hangzhou, China and serves as consultant for Viravaxx and WORG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Nat Rev Immunol. 2006 Oct;6(10):761-71
pubmed: 16998509
J Allergy Clin Immunol. 2010 Apr;125(4):909-917.e4
pubmed: 20226507
Curr Allergy Asthma Rep. 2018 Jun 9;18(7):39
pubmed: 29886521
J Allergy Clin Immunol. 2017 Dec;140(6):1485-1498
pubmed: 29221580
Allergy. 2021 Jan;76(1):131-149
pubmed: 32249442
Biopolymers. 1996 Mar;38(3):305-20
pubmed: 8906967
Front Immunol. 2021 Mar 08;12:651500
pubmed: 33763086
J Allergy Clin Immunol. 2020 Nov;146(5):1097-1108
pubmed: 32298697
J Allergy Clin Immunol. 2011 Jul;128(1):178-184.e7
pubmed: 21513971
Sci Rep. 2017 Sep 22;7(1):12135
pubmed: 28939849
FASEB J. 1999 May;13(8):843-56
pubmed: 10224228
World Allergy Organ J. 2017 Apr 18;10(1):14
pubmed: 28451053
J Allergy Clin Immunol. 2017 Feb;139(2):541-549.e8
pubmed: 27793411
Allergy. 2019 Dec;74(12):2461-2478
pubmed: 31228873
J Allergy Clin Immunol. 2014 Mar;133(3):836-45.e11
pubmed: 24182774
Allergy. 2004 Jan;59(1):65-73
pubmed: 14674936
Int Arch Allergy Immunol. 2013;160(3):233-40
pubmed: 23075813
J Allergy Clin Immunol. 2015 May;135(5):1207-7.e1-11
pubmed: 25441634
Mol Immunol. 2011 Sep;48(15-16):2130-4
pubmed: 21820178
J Allergy Clin Immunol. 2015 Oct;136(4):1083-91
pubmed: 25956509
Clin Exp Allergy. 2019 Jun;49(6):808-818
pubmed: 30734376
Adv Immunol. 2018;138:195-256
pubmed: 29731005
Immunol Lett. 2017 Sep;189:19-26
pubmed: 28472641
Eur J Clin Invest. 2008 Dec;38(12):959-65
pubmed: 19021722
Int Arch Allergy Immunol. 1997 Sep;114(1):59-67
pubmed: 9303332
Curr Allergy Asthma Rep. 2016 Sep;16(9):69
pubmed: 27600386
Allergy. 2018 Aug;73(8):1653-1661
pubmed: 29319884
Int Arch Allergy Immunol. 2012;159(3):253-62
pubmed: 22722650
J Allergy Clin Immunol. 2016 Feb;137(2):351-7
pubmed: 26853127
Allergy. 2008 Jun;63(6):758-67
pubmed: 18445190
J Immunol. 2013 Apr 1;190(7):3059-67
pubmed: 23460742
World Allergy Organ J. 2020 Apr 29;13(5):100118
pubmed: 32373267
Int Arch Allergy Immunol. 2008;147(2):101-9
pubmed: 18520154
Clin Exp Allergy. 2016 Feb;46(2):365-76
pubmed: 26602749
Clin Exp Allergy. 2004 Oct;34(10):1525-33
pubmed: 15479266
Allergy. 2021 Jul;76(7):2177-2188
pubmed: 33484161
Chem Immunol Allergy. 2014;100:234-42
pubmed: 24925403
FASEB J. 2001 Sep;15(11):2042-4
pubmed: 11511525
J Allergy Clin Immunol. 2019 Mar;143(3):1248-1252.e12
pubmed: 30445063
J Allergy Clin Immunol. 2018 Nov;142(5):1656-1659.e9
pubmed: 30059698
FASEB J. 1992 Nov;6(14):3265-74
pubmed: 1385242