Roles of structure and structural dynamics in the antibody recognition of the allergen proteins: an NMR study on Blomia tropicalis major allergen.
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 alpha 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.
Naik
Mandar T
MT
Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
Chang
Chi-Fon
CF
Kuo
I-Chun
IC
Kung
Camy C-H
CC
Yi
Fong-Cheng
FC
Chua
Kaw-Yan
KY
Huang
Tai-Huang
TH
D000485:Allergens / Q000737:chemistry* / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D001666:Binding Sites, Antibody; D017124:Conserved Sequence; D000939:Epitopes / Q000032:analysis / Q000737:chemistry; D007073:Immunoglobulin E / Q000737:chemistry; D019476:Insect Proteins / Q000737:chemistry* / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D008925:Mites / Q000276:immunology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation
D000485:Allergens; D000939:Epitopes; D019476:Insect Proteins; D007073:Immunoglobulin E