8F60

anti-BTLA monoclonal antibody r23C8 in complex with BTLA

8F60 の概要

• エントリーDOI: 10.2210/pdb8f60/pdb
• 分子名称: r23C8 Fab heavy chain, r23C8 Fab light chain, B- and T-lymphocyte attenuator, ... (6 entities in total)
• 機能のキーワード: monoclonal antibody, immune system
• 由来する生物種: Oryctolagus cuniculus; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 61664.45

構造登録者

Hendle, J.,Atwell, S.,Lieu, R.,Hickey, M.,Weichert, K. (登録日: 2022-11-15, 公開日: 2023-05-24, 最終更新日: 2024-11-20)

主引用文献

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

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: 37279757
DOI: 10.1016/j.str.2023.05.011

実験手法

X-RAY DIFFRACTION (1.64 Å)