Development and characterization of a novel anti-IgE monoclonal antibody.
IgE is the central macromolecular mediator responsible for the progression of allergic reactions. Omalizumab (Xolair) is a humanized monoclonal anti-IgE antibody directed at the FcepsilonRI-binding domain of human IgE, which represents a novel therapeutic approach in the management of asthma. In this study, we developed a monoclonal antibody (7A5) against human IgE via hybridoma technique. Our data showed that 7A5 could inhibit free IgE molecules to bind to receptors without affecting IgE already bound to cellular receptors. Importantly, 7A5 was able to inhibit IgE-induced histamine release of basophilic leukemia cells. Next, the phage display peptide library technology was employed to select peptides binding to 7A5 and a striking peptide sequence motif was recovered, which is homologous to the sequence (391)KQR(393) within the Cepsilon3 domain of IgE-Fc, Our results further indicated that 7A5 specifically bound to the synthesized peptide "(388)KEEKQRN(394)" containing the (391)KQR(393) motif in IgE-Fc. The epitope of 7A5 was found to be spatially close to the FcepsilonRI-binding site, suggesting that 7A5 binding to IgE might block IgE binding to receptors via steric hindrance. The anti-IgE monoclonal antibody 7A5 may have the potential to be developed as a therapeutic agent for the treatment of allergic diseases.
Qian
Weizhu
W
International Joint Cancer Institute, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, People's Republic of China.
Zhang
Xunmin
X
Li
Bohua
B
Zhang
Dapeng
D
Tong
Qing
Q
Chen
Lin
L
Zheng
Lei
L
Kou
Geng
G
Wang
Hao
H
Hou
Sheng
S
Guo
Yajun
Y
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*; D045744:Cell Line, Tumor; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D019151:Peptide Library; D010455:Peptides / Q000276:immunology; D011487:Protein Conformation; D051381:Rats; D017455:Receptors, IgE / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D019151:Peptide Library; D010455:Peptides; D017455:Receptors, IgE; C026408:anti-IgE antibodies; D007073:Immunoglobulin E