Epitopes described in "Epitope mapping and in silico characterization of interactions between Der p 7 allergen and MoAb WH9."

Article Authors:Hsiao-Yun Tai; Jia-Kai Zhou; Hong Chou; Ming F Tam; Yu-Sen Chen; Sheh-Yi Sheu; Horng-Der Shen
Article Title:Epitope mapping and in silico characterization of interactions between Der p 7 allergen and MoAb WH9.
Reference Detail
Reference ID:1026662
Abstract:Der p 7 is an important house dust mite allergen. However, antigenic determinants of Der p 7 are largely unknown. The purpose of this study is to analyze the determinants of Der p 7 and determine the structural basis of interactions between Der p 7 and WH9, an IgE-binding inhibition mouse monoclonal antibody (MoAb). IgE and WH9-reactive determinant(s) was identified by immunoblot using allergen mutants. A 3-D binary complex structure of Der p 7 and WH9 was simulated with homology modeling and docking methods. Our results obtained showed that among the five Der p 7 mutants (S156A, I157A, L158A, D159A, P160A), serum no. 1045 with IgE-binding against Der p 7 exhibited a reduced IgE immunoblot reactivity against Der p 7 L158A and D159A mutants. WH9 showed reduced immunoblot reactivity against S156A, L158A, D159A and P160A and the observation was confirmed by immunoblot inhibition. The WH9-binding determinant on Der p 7 containing S156, L158, D159 and P160 assumes a loop-like structure. The structural model of the Der p 7-WH9 complex suggests residues S156, I157, L158, D159 and P160 of Der p 7 contribute to WH9 binding via potential hydrogen bonds, electrostatic and hydrophobic interactions. In conclusion, MoAb WH9 interacts with critical residues L158 and D159 of Der p 7 and inhibits IgE-binding to Der p 7. Results obtained advance our understanding on molecular and structural bases of the antigenicity of Der p 7, its interactions with MoAb WH9 and facilitate the design of safer immunotherapy of human atopic disorders.
Affiliations:Department of Medical Research and Education, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Reference Type:Literature
PubMed ID:23940735
Journal:PLoS One
Journal Volume:8
Article Pages:e71269
Journal ISSN:1932-6203
Article Chemical List:Antibodies, Monoclonal;Antigens, Dermatophagoides;Arthropod Proteins;Dermatophagoides pteronyssinus antigen p 7;Immunoglobulin E
Article MeSH List:Amino Acid Sequence; Animals; Antibodies, Monoclonal(chemistry; metabolism); Antigens, Dermatophagoides(chemistry; genetics; immunology); Arthropod Proteins(chemistry; genetics; immunology); Cells, Cultured; Computational Biology; Epitope Mapping(methods); Humans; Immunoglobulin E(immunology; metabolism); Molecular Docking Simulation; Molecular Sequence Data; Mutagenesis, Site-Directed; Protein Binding; Protein Interaction Maps(immunology)
Curation Last Updated:2015-06-05 04:07:41