9JQT

Structure of interleukin receptor common gamma chain (IL2Rgamma/CD132) in complex with 2D4

9JQT の概要

• エントリーDOI: 10.2210/pdb9jqt/pdb
• EMDBエントリー: 61741
• 分子名称: Cytokine receptor common subunit gamma, 2D4-Heavy Chain, 2D4-Light Chain, ... (4 entities in total)
• 機能のキーワード: il2rg, cd132, il-2, 2d4, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 88918.79

構造登録者

Lu, Q.J.,Yin, H.Q. (登録日: 2024-09-28, 公開日: 2024-12-18)

主引用文献

Yin, H.,Li, L.,Feng, X.,Wang, Z.,Zheng, M.,Zhao, J.,Fan, X.,Wu, W.,Gao, L.,Zhan, Y.,Zhao, M.,Lu, Q.
2D4, a humanized monoclonal antibody targeting CD132, is a promising treatment for systemic lupus erythematosus.
Signal Transduct Target Ther, 9:323-323, 2024

PubMed Abstract: Current therapies for systemic lupus erythematosus that target a particular factor or cell type exhibit limited effectiveness. To address this limitation, our focus was on CD132, a subunit common to six inflammatory factor receptors implicated in SLE. Our study revealed heightened CD132 expression in SLE patients' lymphocytes, contributing to the production of pro-inflammatory cytokines and immunoglobulins. We developed a novel humanized anti-CD132 monoclonal antibody, named as 2D4. 2D4 efficiently blocked IL-21 and IL-15, with limited effectiveness against IL-2, thereby suppressing T and B cells without disrupting immune tolerance. In the mouse immunization model, 2D4 virtually inhibited T cell-dependent, antigen-specific B-cell response. In lupus murine models, 2D4 mitigated inflammation by suppressing multiple pro-inflammatory cytokines and anti-dsDNA antibody titers, also diminishing proteinuria and glomerulonephritis. Compared to Belimumab, 2D4 exhibited superior efficacy in ameliorating the inflammatory state and preserving renal function. Moreover, 2D4 exhibited the ability to inhibit the production of pro-inflammatory factors and autoantibodies in PBMCs from individuals with SLE, highlighting its therapeutic potential for SLE individuals. Potent, 2D4 has the potential to significantly improve clinical outcomes in SLE and other complex autoimmune disorders.

PubMed: 39551768
DOI: 10.1038/s41392-024-02017-6

実験手法

ELECTRON MICROSCOPY (2.7 Å)