8F6L

anti-BTLA monoclonal antibody h25F7 in complex with BTLA

Summary for 8F6L

• Entry DOI: 10.2210/pdb8f6l/pdb
• Related: 8F60
• Descriptor: h25F7 Fab heavy chain, h25F7 Fab light chain, B- and T-lymphocyte attenuator, ... (4 entities in total)
• Functional Keywords: monoclonal antibody, complex, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 63694.84

Authors

Hendle, J.,Atwell, S.,Lieu, R.,Hickey, M.,Weichert, K. (deposition date: 2022-11-16, release date: 2023-05-24, Last modification date: 2024-10-16)

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

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

Experimental method

X-RAY DIFFRACTION (1.85 Å)