Open Access

Identification of immunodominant IgE epitopes of the major house dust mite allergen Der f 24

  • Authors:
    • Ze‑Lang Cai
    • Zhen Zhang
    • Wen‑Li Luo
    • Yi‑Bo Hou
    • Yong‑Shen He
    • Jia‑Jie Chen
    • Kunmei Ji
  • View Affiliations

  • Published online on: September 18, 2019     https://doi.org/10.3892/ijmm.2019.4345
  • Pages: 1888-1898
  • Copyright: © Cai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Previously, a ubiquinol‑cytochrome c reductase binding protein (UQCRB) homolog was identified in the house dust mite (HDM) species Dermatophagoides farinae (Der f) as a major allergen. In the present study, the immunodominant immunoglobulin E (IgE) epitope of the protein Der f 24 was investigated. Analysis of the homologous amino acid (aa) sequences in Der f and human UQCRB was performed. Four different recombinant Der f 24 and hybrid proteins formed by integrating Der f and human UQCRB sequences were expressed in Escherichia coli, purified using Ni‑NTA resins, and IgE‑binding activity was determined using IgE‑western blotting and enzyme‑linked immunosorbent assay (ELISA) experiments. IgE epitopes were further identified by IgE‑dot blotting and IgE‑ELISA with synthetic polypeptides and HDM‑allergic sera. Three‑dimensional (3D) structural modeling was used to analyze the position of the immunodominant IgE epitope. The amino acid sequence homology between Der f 24 and the human UQCRB protein was determined to be 39.34%. IgE‑ELISA and western blot analysis showed that all of the Der f‑human UQCRB hybrid proteins generated, except for the one lacking 59 residues of the N‑terminal region of Der f 24, were bound by allergic serum IgE. A synthetic polypeptide consisting of 32 residues of the N‑terminal reacted with IgEs from HDM‑allergic sera and could be used to generate high titer specific IgG or specific IgE antibodies in immunized mice. The 32‑aa N‑terminal region of Der f 24 was localized to a structural protrusion, which may facilitate specific IgE‑binding. These results indicate that the immunodominant IgE epitope of Der f 24 is located mainly in a 32‑residue region of the N‑terminus. These findings may inform the mechanisms of HDM allergy sensitization and allergy immunotherapy development.

References

1 

D'Amato G, Liccardi G, D'Amato M and Holgate S: Environmental risk factors and allergic bronchial asthma. Clin Exp Allergy. 35:1113–1124. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Ciprandi G, Puccinelli P, Incorvaia C and Passalacqua G: Italian Cometa Study Group: The relevance of house dust mites allergy in clinical practice: The epidemiological impact on allergen immunotherapy. Immunotherapy. 9:1219–1224. 2017. View Article : Google Scholar : PubMed/NCBI

3 

Bousquet PJ, Chinn S, Janson C, Kogevinas M, Burney P and Jarvis D: European Community Respiratory Health Survey I: Geographical variation in the prevalence of positive skin tests to environmental aeroallergens in the European community respiratory health survey I. Allergy. 62:301–309. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Chew GL, Reardon AM, Correa JC, Young M, Acosta L, Mellins R, Chew FT and Perzanowski MS: Mite sensitization among Latina women in New York, where dust-mite allergen levels are typically low. Indoor Air. 19:193–197. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Yang L and Zhu R: Immunotherapy of house dust mite allergy. Hum Vaccin Immunother. 13:2390–2396. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Pomés A, Davies JM, Gadermaier G, Hilger C, Holzhaouser T, Lidholm J, Lopata AL, Mueller GA, Nandy A, Radauer C, et al: WHO/IUIS allergen nomenclature: Providing a common language. Mol Immunol. 100:3–13. 2018. View Article : Google Scholar : PubMed/NCBI

7 

Thomas WR, Smith WA, Hales BJ, Mills KL and O'Brien RM: Characterization and immunobiology of house dust mite allergens. Int Arch Allergy Immunol. 129:1–18. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Weghofer M, Grote M, Resch Y, Casset A, Kneidinger M, Kopec J, Thomas WR, Fernández-Caldas E, Kabesch M, Ferrara R, et al: Identification of Der p 23, a peritrophin-like protein, as a new major Dermatophagoides pteronyssinus allergen associated with the peritrophic matrix of mite fecal pellets. J Immunol. 190:3059–3067. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Chan TF, Ji KM, Yim AK, Liu XY, Zhou JW, Li RQ, Yang KY, Li J, Li M, Law PT, et al: The draft genome, transcriptome, and microbiome of Dermatophagoides farinae reveal a broad spectrum of dust mite allergens. J Allergy Clin Immunol. 135:539–548. 2015. View Article : Google Scholar

10 

Gough L, Schulz O, Sewell HF and Shakib F: The cysteine protease activity of the major dust mite allergen Der p 1 selectively enhances the immunoglobulin E antibody response. J Exp Med. 190:1897–902. 1999. View Article : Google Scholar : PubMed/NCBI

11 

Gough L, Sewell HF and Shakib F: The proteolytic activity of the major dust mite allergen Der p 1 enhances the IgE antibody response to a bystander antigen. Clin Exp Allergy. 31:1594–1598. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Trompette A, Divanovic S, Visintin A, Blanchard C, Hegde RS, Madan R, Thorne PS, Wills-Karp M, Gioannini TL, Weiss JP and Karp CL: Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature. 457:585–588. 2009. View Article : Google Scholar

13 

Park BS, Lee NR, Kim MJ, Kim SY and Kim IS: Interaction of Der p 2 with Toll-like receptor 4 and its effect on cytokine secretion. Biomed Sci Letters. 21:152–159. 2015. View Article : Google Scholar

14 

Hales BJ, Martin AC, Pearce LJ, Laing IA, Hayden CM, Goldblatt J, Le Souef PN and Thomas WR: IgE and IgG anti-house dust mite specificities in allergic disease. J Allergy Clin Immunol. 118:361–367. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Jacquet A: Innate immune responses in house dust mite allergy. ISRN Allergy. 2013.735031:2013.

16 

Amin K: The role of mast cells in allergic inflammation. Respir Med. 106:9–14. 2012. View Article : Google Scholar

17 

Pomes A: Relevant B cell epitopes in allergic disease. Int Arch Allergy Immunol. 152:1–11. 2010. View Article : Google Scholar :

18 

Matsuo H, Yokooji T and Taogoshi T: Common food allergens and their IgE-binding epitopes. Allergol Int. 64:332–343. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Bronnert M, Mancini J, Birnbaum J, Agabriel C, Liabeuf V, Porri F, Cleach I, Fabre A, Deneux I, Grandné V, et al: Component-resolved diagnosis with commercially available D. pteronyssinus Der p 1 Der p 2 and Der p 10: Relevant markers for house dust mite allergy. Clin Exp Allergy. 42:1406–1415. 2012. View Article : Google Scholar

20 

Chou H, Tam MF, Lee SS, Tang RB, Lin TH, Tai HY, Chen YS and Shen HD: Asp159 is a critical core amino acid of an IgE-binding and cross-reactive epitope of a dust mite allergen Der f 7. Mol Immunol. 48:2130–2134. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Chruszcz M, Chapman MD, Vailes LD, Stura EA, Saint-Remy JM, Minor W and Pomes A: Crystal structures of mite allergens Der f 1 and Der p 1 reveal differences in surface-exposed residues that may influence antibody binding. J Mol Biol. 386:520–530. 2009. View Article : Google Scholar : PubMed/NCBI

22 

de Halleux S, Stura E, VanderElst L, Carlier V, Jacquemin M and Saint-Remy JM: Three-dimensional structure and IgE-binding properties of mature fully active Der p 1, a clinically relevant major allergen. J Allergy Clin Immunol. 117:571–576. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Takai T, Kato T, Yasueda H, Okumura K and Ogawa H: Analysis of the structure and allergenicity of recombinant pro- and mature Der p 1 and Der f 1: Major conformational IgE epitopes blocked by prodomains. J Allergy Clin Immunol. 115:555–563. 2005. View Article : Google Scholar : PubMed/NCBI

24 

Cho YS, Jung HJ, Seok SH, Payumo AY, Chen JK and Kwon HJ: Functional inhibition of UQCRB suppresses angiogenesis in zebrafish. Biochem Biophys Res Commun. 433:396–400. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Cai ZL, Chen JJ, Zhang Z, Hou YB, He YS, Sun JL and Ji K: Identification of immunodominant IgE binding epitopes of Der p 24, a major allergen of Dermatophagoides pteronyssinus. Clin Transl Allergy. 9:282019. View Article : Google Scholar :

26 

Chen ZG, Li YT, Wang WH, Tan KS, Zheng R, Yang LF, Guan WJ, Hong HY and Yang QT: Distribution and determinants of dermatophagoides mites sensitization of allergic rhinitis and allergic asthma in China. Int Arch Allergy Immunol. 180:17–27. 2019. View Article : Google Scholar

27 

Thomas WR: Geography of house dust mite allergens. Asian Pac J Allergy Immunol. 28:211–224. 2010.

28 

Liu XY, Ji KM, Gao B and Liu ZG: Expression, purification and identification of the recombinant allergen Der p2 from Dermatophagoides pteronyssinus and investigation on its immunological activities. Chin J Zoonoses. 009:929–935. 2009.

29 

Lauber B, Molitor V, Meury S, Doherr MG, Favrot C, Tengvall K, Bergvall K, Leeb T, Roosje P and Marti E: Total IgE and allergen-specific IgE and IgG antibody levels in sera of atopic dermatitis affected and non-affected Labrador- and Golden retrievers. Vet Immunol Immunopathol. 149:112–118. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Taylor JA, Karas JL, Ram MK, Green OM and Seidel-Dugan C: Activation of the high-affinity immunoglobulin E receptor Fc epsilon RI in RBL-2H3 cells is inhibited by Syk SH2 domains. Mol Cell Biol. 15:4149–4157. 1995. View Article : Google Scholar : PubMed/NCBI

31 

Zhang Q, Wang P, Kim Y, Haste-Andersen P, Beaver J, Bourne PE, Bui HH, Buus S, Frankild S, Greenbaum J, et al: Immune epitope database analysis resource (IEDB-AR). Nucleic Acids Res. 36:Web Server Issue. pp. W513–W518. 2008, View Article : Google Scholar : PubMed/NCBI

32 

Costa MA, Duro G, Izzo V, Colombo P, Mirisola MG, Locorotondo G, Cocchiara R and Geraci D: The IgE-binding epitopes of rPar j 2, a major allergen of Parietaria judaica pollen, are heterogeneously recognized among allergic subjects. Allergy. 55:246–250. 2000. View Article : Google Scholar

33 

Banerjee B, Greenberger PA, Fink JN and Kurup VP: Conformational and linear B-cell epitopes of Asp f 2, a major allergen of Aspergillus fumigatus, bind differently to immuno-globulin E antibody in the sera of allergic bronchopulmonary aspergillosis patients. Infect Immun. 67:2284–2291. 1999.PubMed/NCBI

34 

Szalai K, Fuhrmann J, Pavkov T, Scheidl M, Wallmann J, Brämswig KH, Vrtala S, Scheiner O, Keller W, Saint-Remy JM, et al: Mimotopes identify conformational B-cell epitopes on the two major house dust mite allergens Der p 1 and Der p 2. Mol Immunol. 45:1308–1317. 2008. View Article : Google Scholar

35 

Stanley JS, King N, Burks AW, Huang SK, Sampson H, Cockrell G, Helm RM, West CM and Bannon GA: Identification and mutational analysis of the immunodominant IgE binding epitopes of the major peanut allergen Ara h 2. Arch Biochem Biophys. 34:244–253. 1997. View Article : Google Scholar

36 

Laskowski RA, MacArthur MW, Moss DS and Thornton JM: PROCHECK-a program to check the stereochemical quality of protein structures. J App Cryst. 26:283–291. 1993. View Article : Google Scholar

37 

Ramos JD, Cheong N, Lee BW and Chua KY: Peptide mapping of immunoglobulin E and immunoglobulin G immunodominant epitopes of an allergenic Blomia tropicalis paramyosin, Blo t 11. Clin Exp Allergy. 33:511–517. 2003. View Article : Google Scholar : PubMed/NCBI

38 

Jung HJ, Kim KH, Kim ND, Han G and Kwon HJ: Identification of a novel small molecule targeting UQCRB of mitochondrial complex III and its anti-angiogenic activity. Bioorg Med Chem Lett. 21:1052–1056. 2011. View Article : Google Scholar : PubMed/NCBI

39 

Greene WK and Thomas WR: IgE binding structures of the major house dust mite allergen Der p I. Mol Immunol. 29:257–262. 1992. View Article : Google Scholar : PubMed/NCBI

40 

Van't Hof W, Driedijk PC, van den Berg M, Beck-Sickinger AG, Jung G and Aalberse RC: Epitope mapping of the Dermatophagoides pteronyssinus house dust mite major allergen Der p II using overlapping synthetic peptides. Mol Immunol. 28:1225–1232. 1991. View Article : Google Scholar

41 

Herrick CA, MacLeod H, Glusac E, Tigelaar RE and Bottomly K: Th2 responses induced by epicutaneous or inhalational protein exposure are differentially dependent on IL-4. J Clin Invest. 105:765–775. 2000. View Article : Google Scholar : PubMed/NCBI

42 

Moingeon P and Mascarell L: Novel routes for allergen immuno-therapy: Safety, efficacy and mode of action. Immunotherapy. 4:201–212. 2012. View Article : Google Scholar : PubMed/NCBI

43 

Chen KW, Blatt K, Thomas WR, Swoboda I, Valent P, Valenta R and Vrtala S: Hypoallergenic Der p 1/Der p 2 combination vaccines for immunotherapy of house dust mite allergy. J Allergy Clin Immunol. 130:435–443. 2012. View Article : Google Scholar : PubMed/NCBI

44 

Winther L, Arnved J, Malling HJ, Nolte H and Mosbech H: Side-effects of allergen-specific immunotherapy: A prospective multi-centre study. Clin Exp Allergy. 36:254–260. 2006. View Article : Google Scholar : PubMed/NCBI

45 

Nishiyama C, Fukada M, Usui Y, Iwamoto N, Yuuki T, Okumura Y and Okudaira H: Analysis of the IgE-epitope of Der f 2, a major mite allergen, by in vitro mutagenesis. Mol Immunol. 32:1021–1029. 1995. View Article : Google Scholar : PubMed/NCBI

46 

Ferreira F, Wallner M, Breiteneder H, Hartl A, Thalhamer J and Ebner C: Genetic engineering of allergens: Future therapeutic products. Int Arch Allergy Immunol. 128:171–178. 2002. View Article : Google Scholar : PubMed/NCBI

47 

Fanuel S, Tabesh S, Mokhtarian K, Saroddiny E, Fazlollahi MR, Pourpak Z, Falak R and Kardar GA: Construction of a recombinant B-cell epitope vaccine based on a Der p1-derived hypoallergen: A bioinformatics approach. Immunotherapy. 10:537–553. 2018. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

November 2019
Volume 44 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Cai, Z., Zhang, Z., Luo, W., Hou, Y., He, Y., Chen, J., & Ji, K. (2019). Identification of immunodominant IgE epitopes of the major house dust mite allergen Der f 24. International Journal of Molecular Medicine, 44, 1888-1898. https://doi.org/10.3892/ijmm.2019.4345
MLA
Cai, Z., Zhang, Z., Luo, W., Hou, Y., He, Y., Chen, J., Ji, K."Identification of immunodominant IgE epitopes of the major house dust mite allergen Der f 24". International Journal of Molecular Medicine 44.5 (2019): 1888-1898.
Chicago
Cai, Z., Zhang, Z., Luo, W., Hou, Y., He, Y., Chen, J., Ji, K."Identification of immunodominant IgE epitopes of the major house dust mite allergen Der f 24". International Journal of Molecular Medicine 44, no. 5 (2019): 1888-1898. https://doi.org/10.3892/ijmm.2019.4345