9B7B

Crystal structure of humanized 44H10 Fab Version 22 in complex with HLA-DR (HLA-DRA*01:01/HLA-DRB1*04:01)

9B7B の概要

• エントリーDOI: 10.2210/pdb9b7b/pdb
• 分子名称: HLA class II histocompatibility antigen, DR alpha chain, Hemagglutinin HA1 chain, HLA class II histocompatibility antigen DR beta chain, h44H10-V22 Antibody, heavy chain, ... (6 entities in total)
• 機能のキーワード: antibody, humanized, mhc class ii, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 191261.77

構造登録者

Kassardjian, A.,Julien, J.P. (登録日: 2024-03-27, 公開日: 2024-08-07, 最終更新日: 2024-10-30)

主引用文献

Kassardjian, A.,Ivanochko, D.,Barber, B.,Jetha, A.,Julien, J.P.
Humanization of Pan-HLA-DR mAb 44H10 Hinges on Critical Residues in the Antibody Framework.
Antibodies, 13:-, 2024

PubMed Abstract: Reducing the immunogenicity of animal-derived monoclonal antibodies (mAbs) for use in humans is critical to maximize therapeutic effectiveness and preclude potential adverse events. While traditional humanization methods have primarily focused on grafting antibody Complementarity-Determining Regions (CDRs) on homologous human antibody scaffolds, framework regions can also play essential roles in antigen binding. Here, we describe the humanization of the pan-HLA-DR mAb 44H10, a murine antibody displaying significant involvement of the framework region in antigen binding. Using a structure-guided approach, we identify and restore framework residues that directly interact with the antigen or indirectly modulate antigen binding by shaping the antibody paratope and engineer a humanized antibody with affinity, biophysical profile, and molecular binding basis comparable to that of the parental 44H10 mAb. As a humanized molecule, this antibody holds promise as a scaffold for the development of MHC class II-targeting therapeutics and vaccines.

PubMed: 39051333
DOI: 10.3390/antib13030057

実験手法

X-RAY DIFFRACTION (3.08 Å)