Roles of Structure and Structural Dynamics in the Antibody Recognition of the Allergen Proteins: An NMR Study on Blomia tropicalis Major Allergen

• Published in: Structure (London) Vol. 16; no. 1; pp. 125 - 136
• Main Authors: Naik, Mandar T., Chang, Chi-Fon, Kuo, I.-Chun, Kung, Camy C.-H., Yi, Fong-Cheng, Chua, Kaw-Yan, Huang, Tai-Huang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.01.2008
• Subjects: Allergens; Allergens - chemistry; Allergens - immunology; Amino Acid Sequence; Animals; Binding Sites, Antibody; Blomia tropicalis; Conserved Sequence; Epitopes - analysis; Epitopes - chemistry; Immunoglobulin E - chemistry; Insect Proteins - chemistry; Insect Proteins - immunology; Magnetic Resonance Spectroscopy; Mites - immunology; Models, Molecular; Molecular Sequence Data; MOLIMMUNO; Protein Conformation; PROTEINS; PROTEINS; MOLIMMUNO
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2007.10.022

Blo t 5 is the major allergen from Blomia tropicalis mites and shows strong IgE reactivity with up to 90% of asthmatic and rhinitis patients' sera. The NMR solution structure of Blo t 5 comprises three long α helices, forming a coiled-coil, triple-helical bundle with a left-handed twist. TROSY-NMR experiments were used to study Blo t 5 interaction with the Fab′ of a specific monoclonal antibody, mAb 4A7. The mAb epitope comprises two closely spaced surfaces, I and II, connected by a sharp turn and bearing critical residues Asn46 and Lys47 on one surface, and Lys54 and Arg57 on the other. This discontinuous epitope overlaps with the human IgE epitope(s) of Blo t 5. Epitope surface II is further predicted to undergo conformational exchange in the millisecond to microsecond range. The results presented are critical for the design of a hypoallergenic Blo t 5 for efficacious immunotherapy of allergic diseases.