9JQT
Structure of interleukin receptor common gamma chain (IL2Rgamma/CD132) in complex with 2D4
Summary for 9JQT
| Entry DOI | 10.2210/pdb9jqt/pdb |
| EMDB information | 61741 |
| Descriptor | Cytokine receptor common subunit gamma, 2D4-Heavy Chain, 2D4-Light Chain, ... (4 entities in total) |
| Functional Keywords | il2rg, cd132, il-2, 2d4, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 88918.79 |
| Authors | |
| Primary citation | 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 Cited by 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: 39551768DOI: 10.1038/s41392-024-02017-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.7 Å) |
Structure validation
Download full validation report
