8F60
anti-BTLA monoclonal antibody r23C8 in complex with BTLA
Summary for 8F60
| Entry DOI | 10.2210/pdb8f60/pdb |
| Descriptor | r23C8 Fab heavy chain, r23C8 Fab light chain, B- and T-lymphocyte attenuator, ... (6 entities in total) |
| Functional Keywords | monoclonal antibody, immune system |
| Biological source | Oryctolagus cuniculus More |
| Total number of polymer chains | 3 |
| Total formula weight | 61664.45 |
| Authors | Hendle, J.,Atwell, S.,Lieu, R.,Hickey, M.,Weichert, K. (deposition date: 2022-11-15, release date: 2023-05-24, Last modification date: 2024-11-20) |
| Primary citation | Cheung, T.C.,Atwell, S.,Bafetti, L.,Cuenca, P.D.,Froning, K.,Hendle, J.,Hickey, M.,Ho, C.,Huang, J.,Lieu, R.,Lim, S.,Lippner, D.,Obungu, V.,Ward-Kavanagh, L.,Weichert, K.,Ware, C.F.,Vendel, A.C. Epitope topography of agonist antibodies to the checkpoint inhibitory receptor BTLA. Structure, 31:958-, 2023 Cited by PubMed Abstract: B and T lymphocyte attenuator (BTLA) is an attractive target for a new class of therapeutics that attempt to rebalance the immune system by agonizing checkpoint inhibitory receptors (CIRs). Herpesvirus entry mediator (HVEM) binds BTLA in both trans- and cis-orientations. We report here the development and structural characterization of three humanized BTLA agonist antibodies, 22B3, 25F7, and 23C8. We determined the crystal structures of the antibody-BTLA complexes, showing that these antibodies bind distinct and non-overlapping epitopes of BTLA. While all three antibodies activate BTLA, 22B3 mimics HVEM binding to BTLA and shows the strongest agonistic activity in functional cell assays and in an imiquimod-induced mouse model of psoriasis. 22B3 is also capable of modulating HVEM signaling through the BTLA-HVEM cis-interaction. The data obtained from crystal structures, biochemical assays, and functional studies provide a mechanistic model of HVEM and BTLA organization on the cell surface and informed the discovery of a highly active BTLA agonist. PubMed: 37279757DOI: 10.1016/j.str.2023.05.011 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.64 Å) |
Structure validation
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