Mapping Mimotopes for House Dust Mite Allergen Der f 7 Using a Specific Monoclonal Antibody

Author(s): Jianglong Peng , Hao Yin , Ying Zhou , Haoyuan Jia , Yubao Cui* .

Journal Name: Protein & Peptide Letters

Volume 26 , Issue 3 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Background: The dust mite Dermatophagoides farinae is a common worldwide cause of indoor allergies induced by its proteins, including the mid-tier allergen Der f 7.

Objective: To identify conformational epitopes in Der f 7 using mimotope mapping and computational modelling.

Methods: Here, we used standard hybridoma technology to generate 3 new monoclonal antibodies against Der f 7 and performed mimotope mapping by probing a random peptide phage display library. Computational tools, including Minox and the DiscoTope-2.0 Server were used to assess the structure and potential position of antigenic residues within Der f 7.

Results: Thirteen mimotopes sharing the common sequence --XX[LST]P[-E][LI]MLPLR[-S]- were identified. Further, computationally-predicted conformational epitopes were found at residues 1-7, 10, 27, 76-81, 92, and 130-133 of Der f 7, and the key amino acids for these epitopes were deduced to be 2P, 3I, 10E, 27E, 78E, 79E, 81I, 130S, and 132E based on the common mimotope sequence.

Conclusion: We identified Der f 7 peptide mimotopes that may model binding sites for blocking antibodies. These may guide the development of immunotherapy for individuals with hypersensitivity to Der f 7.

Keywords: House dust mite allergen, mimotopes, monoclonal antibody, random peptide library, Der f 7, indoor allergies.

Szalai, K.; Fuhrmann, J.; Pavkov, T.; Scheidl, M.; Wallmann, J.; Brämswig, K.H.; Vrtala, S.; Scheiner, O.; Keller, W.; Saint-Remy, J.M. Mimotopes identify conformational B-cell epitopes on the two major house dust mite allergens Der p 1 and Der p 2. Mol. Immunol., 2008, 45, 1308-1317.
Li, J.; Sun, B.; Huang, Y.; Lin, X.; Zhao, D.; Tan, G.; Wu, J.; Zhao, H.; Cao, L.; Zhong, N. China alliance of research on respiratory allergic disease. A multicentre study assessing the prevalence of sensitizations in patients with asthma and/or rhinitis in China. Allergy, 2009, 64, 1083-1092.
Thomas, W.R.; Heinrich, T.K.; Smith, W.A.; Hales, B.J. Pyroglyphid house dust mite allergen. Protein Pept. Lett., 2007, 14, 943-953.
Vrtala, S.; Huber, H.; Thomas, W.R. Recombinant house dust mite allergens. Methods, 2014, 66, 67-74.
Shen, H.D.; Chua, K.Y.; Lin, W.L.; Hsieh, I.M.; Thomas, W.R. Molecular cloning and immunological characterization of the house dust mite allergen Der f 7. Clin. Exp. Allergy, 1995, 25, 1000-1006.
Tovey, E.R. Allergen avoidance. Curr. Allergy Asthma Rep., 2008, 8, 126-132.
Rolland, J.M.; Gardner, L.M.; O’Hehir, R.E. Allergen-related approaches to immunotherapy. Pharmacol. Ther., 2009, 121, 273-284.
Bousquet, J.; Lockey, R.; Mailing, H.J. Allergen immunotherapy: Therapeutic vaccines for allergic diseases. A WHO position paper. J. Allergy Clin. Immunol., 1998, 102, 558-562.
Wachholz, P.A.; Soni, N.K.; Till, S.J.; Durham, S.R. Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy. J. Allergy Clin. Immunol., 2003, 112, 915-922.
Knittelfelder, R.; Riemer, A.B.; Jensen-Jarolim, E. Mimotope vaccination--from allergy to cancer. Expert Opin. Biol. Ther., 2009, 9, 493-506.
Lin, J.; Sampson, H.A. The role of immunoglobulin E-binding epitopes in the characterization of food allergy. Curr. Opin. Allergy Clin. Immunol., 2009, 9, 357-363.
Wallmann, J.; Proell, M.; Stepanoska, T.; Hantusch, B.; Pali-Schöll, I.; Thalhamer, T.; Thalhamer, J.; Jensen-Jarolim, E.; Hartl, A. A mimotope gene encoding the major IgE epitope of allergen Phl p 5 for epitope-specific immunization. Immunol. Lett., 2009, 122, 68-75.
Cui, Y.B.; Cai, H.X.; Zhou, Y.; Gao, C.X.; Shi, W.H.; Yu, M.; Li, L. Cloning, expression and characterization of Der f 7, an allergen of Dermatophagoides farinae from China. J. Med. Entomol., 2010, 47, 868-876.
Cui, Y.; Zhou, P.; Peng, J.; Peng, M.; Zhou, Y.; Lin, Y.; Liu, L. Cloning, sequence analysis, and expression of cDNA coding for the major house dust mite allergen, Der f 1, in Escherichia coli. Braz. J. Med. Biol. Res., 2008, 41, 380-388.
Cui, Y.B.; Cai, H.X.; Li, L.; Zhou, Y.; Gao, C.X.; Shi, W.H.; Yu, M. Cloning, sequence analysis and expression in E. coli of the group 3 allergen of Dermatophgoides farinae. Chin. Med. J., 2009, 122, 2657-2661.
Cui, Y.B.; Zhou, Y.; Mai, G.F.; Yang, L.; Wang, Y.G. Molecular cloning, bioinformatic analysis, and expression of a house dust mite allergen Der f 5 of Dermatophagoides farinae from China. Braz. J. Med. Biol. Res., 2012, 45, 746-752.
Cui, Y.B.; Zhou, Y.; Wang, Y.G.; Ma, G.F.; Yang, L. The group 10 allergen of Dermatophagoides farinae (Acari: Pyroglyphidae): cDNA cloning, sequence analysis, and expression in E. coli BL21. J. Med. Entomol., 2013, 50, 205-208.
Cui, Y.B.; Zhou, Y.; Shi, W.H.; Ma, G.H.; Yang, L.; Wang, Y.G. Cloning, expression, and analysis of the group 2 allergen from Dermatophagoides farinae from China. An. Acad. Bras. Cienc., 2010, 82, 1-11.
Cui, Y.; Zhou, Y.; Shi, W.; Ma, G.; Yang, L.; Wang, Y.; Li, L. Molecular cloning, expression, sequence analyses of dust mite allergen Der f 6 and its IgE-binding reactivity with mite allergic asthma patients in southeast China. Mol. Biol. Rep., 2012, 39, 961-968.
Cui, Y.; Jiang, Y.; Ji, Y.; Zhou, Y.; Yu, L.; Wang, N.; Li, Y.; Zhang, C. Cloning, expression, and analysis of a cDNA coding for the Dermatophagoides farinae group 21 (Der f 21) allergen. Am. J. Transl. Res., 2014, 6, 786-792.
Cui, Y.; Yu, L.; Zhou, Y.; Yang, L.; Zhang, C. Mimotope identification of dust mite allergen Der f 5 using phage-displayed random peptide libraries. Mol. Med. Rep., 2016, 14, 4816-4822.
Chapman, M.D.; Heymann, P.W.; Wilkins, S.R.; Brown, M.J.; Platts-Mills, T.A. Monoclonal immunoassays for major dust mite (Dermatophagoides) allergens, Der p 1 and Der f 1, and quantitative analysis of the allergen content of mite and house dust extracts. J. Allergy Clin. Immunol., 1987, 80, 184-194.
Akagawa, M.; Mori, T.; Ando, T.; Okudaira, H. Preparation of specific monoclonal antibodies against Der f 2, one of the major allergens of Dermatophagoides farinae. Jpn. J. Allergol., 1991, 40, 1239-1242.
Yong, T.S.; Lee, S.M.; Park, G.M.; Lee, I.Y.; Ree, H.I.; Kim, K.S.; Oh, S.H.; Park, J.W.; Hong, C.S. Monoclonal antibodies to recombinant Der p 2, a major house dust mite allergen: Specificity, epitope analysis and development of two-site capture ELISA. Korean J. Parasitol., 1999, 37, 163-169.
Jeong, K.Y.; Jin, H.S.; Oh, S.H.; Hong, C.S.; Lee, I.Y.; Ree, I.Y.; Ree, H.I.; Yong, T.S. Monoclonal antibodies to recombinant Der f 2 and development of a two-site ELISA sensitive to major Der f 2 isoallergen in Korea. Allergy, 2002, 57, 29-34.
Schöll, I.; Wiedermann, U.; Förster-Waldl, E.; Ganglberger, E.; Baier, K.; Boltz-Nitulescu, G.; Scheiner, O.; Ebner, C.; Jensen-Jarolim, E. Phage-displayed Bet mim 1, a mimotope of the major birch pollen allergen Bet v 1, induces B cell responses to the natural antigen using bystander T cell help. Clin. Exp. Allergy, 2002, 32, 1583-1588.
Wallmann, J.; Epstein, M.M.; Singh, P.; Brunner, R.; Szalai, K.; El-Housseiny, L.; Pali-Schöll, I.; Jensen-Jarolim, E. Mimotope vaccination for therapy of allergic asthma: Anti-inflammatory effects in a mouse model. Clin. Exp. Allergy, 2010, 40, 650-658.
Kringelum, J.V.; Lundegaard, C.; Lund, O.; Nielsen, M.; Reliable, B. Cell epitope predictions: Impacts of method development and improved benchmarking. PLOS Comput. Biol., 2012, 8, e1002829.
Shen, H.D.; Tam, M.F.; Huang, C.H.; Chou, H.; Tai, H.Y.; Chen, Y.S.; Sheu, S.Y.; Thomas, W.R. Homology modeling and monoclonal antibody binding of the Der f 7 dust mite allergen. Immunol. Cell Biol., 2011, 89, 225-230.
Chou, H.; Tam, M.F.; Lee, S.S.; Tang, R.B.; Lin, T.H.; Tai, H.Y.; Chen, Y.S.; Shen, H.D. 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., 2011, 48, 2130-2134.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [184 - 191]
Pages: 8
DOI: 10.2174/0929866526666181208165138
Price: $58

Article Metrics

PDF: 18