3HR5

M1prime peptide from IgE bound by humanized antibody 47H4 Fab

3HR5 の概要

• エントリーDOI: 10.2210/pdb3hr5/pdb
• 分子名称: Fab h47H4 light chain, Fab h47H4 heavy chain, M1prime-derived peptide, ... (5 entities in total)
• 機能のキーワード: fab-peptide complex, immune system
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 208103.77

構造登録者

Eigenbrot, C.W.,Ultsch, M.H. (登録日: 2009-06-08, 公開日: 2010-05-19, 最終更新日: 2024-11-20)

主引用文献

Brightbill, H.D.,Jeet, S.,Lin, Z.,Yan, D.,Zhou, M.,Tan, M.,Nguyen, A.,Yeh, S.,Delarosa, D.,Leong, S.R.,Wong, T.,Chen, Y.,Ultsch, M.,Luis, E.,Ramani, S.R.,Jackman, J.,Gonzalez, L.,Dennis, M.S.,Chuntharapai, A.,DeForge, L.,Meng, Y.G.,Xu, M.,Eigenbrot, C.,Lee, W.P.,Refino, C.J.,Balazs, M.,Wu, L.C.
Antibodies specific for a segment of human membrane IgE deplete IgE-producing B cells in humanized mice.
J.Clin.Invest., 120:2218-2229, 2010

PubMed Abstract: IgE-mediated hypersensitivity is central to the pathogenesis of asthma and other allergic diseases. Although neutralization of serum IgE with IgE-specific antibodies is in general an efficacious treatment for allergic asthma, one limitation of this approach is its lack of effect on IgE production. Here, we have developed a strategy to disrupt IgE production by generating monoclonal antibodies that target a segment of membrane IgE on human IgE-switched B cells that is not present in serum IgE. This segment is known as the M1' domain, and using genetically modified mice that contain the human M1' domain inserted into the mouse IgE locus, we demonstrated that M1'-specific antibodies reduced serum IgE and IgE-producing plasma cells in vivo, without affecting other immunoglobulin isotypes. M1'-specific antibodies were effective when delivered prophylactically and therapeutically in mouse models of immunization, allergic asthma, and Nippostrongylus brasiliensis infection, likely by inducing apoptosis of IgE-producing B cells. In addition, we generated a humanized M1'-specific antibody that was active on primary human cells in vivo, as determined by its reduction of serum IgE levels and IgE plasma cell numbers in a human PBMC-SCID mouse model. Thus, targeting of human IgE-producing B cells with apoptosis-inducing M1'-specific antibodies may be a novel treatment for asthma and allergy.

PubMed: 20458139
DOI: 10.1172/JCI40141

実験手法

X-RAY DIFFRACTION (2.4 Å)