9D72

CryoEM structure of anti-MHC-I Fab M1/42 complex with H2-Dd

9D72 の概要

• エントリーDOI: 10.2210/pdb9d72/pdb
• 関連するPDBエントリー: 8TQ4
• EMDBエントリー: 46600
• 分子名称: Beta-2-microglobulin, Fab M1/42 Light Chain, Surface protein gp120, ... (5 entities in total)
• 機能のキーワード: mhc-i, anti-mouse-mab, h2-dd, m1/42, anti-mhc-i antibody, anti-tumor, cancer immunotherapy, antitumor protein, antitumor protein-immune system complex, antitumor protein/immune system
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 91734.50

構造登録者

Jiang, J.,Natarajan, K.,Margulies, D.H.,Lei, H.,Huang, R. (登録日: 2024-08-16, 公開日: 2026-02-04, 最終更新日: 2026-05-13)

主引用文献

Jiang, J.,Panda, A.K.,Natarajan, K.,Lei, H.,Sharma, S.,Boyd, L.F.,Towler, R.R.,Chempati, S.,Ahmad, J.,Morton, A.J.,Lang, Z.C.,Sun, Y.,Sgourakis, N.,Meier-Schellersheim, M.,Huang, R.K.,Shevach, E.M.,Margulies, D.H.
Structural mechanism of anti-MHC-I antibody blocking of inhibitory NK cell receptors in tumor immunity.
Res Sq, 2025

PubMed Abstract: Anti-major histocompatibility complex class I (MHC-I) mAbs can stimulate immune responses to tumors and infections by blocking suppressive signals delivered via various immune inhibitory receptors. To understand such functions, we determined the structure of a highly cross-reactive anti-human MHC-I mAb, B1.23.2, in complex with the MHC-I molecule HLA-B*44:05 by both cryo-electron microscopy (cryo-EM) and X-ray crystallography. Structural models determined by the two methods were essentially identical revealing that B1.23.2 binds a conserved region on the α2 helix that overlaps the killer immunoglobulin-like receptor (KIR) binding site. Structural comparison to KIR/HLA complexes reveals a mechanism by which B1.23.2 blocks inhibitory receptor interactions, leading to natural killer (NK) cell activation. B1.23.2 treatment of the human KLM-1 pancreatic cancer model in humanized (NSG-IL15) mice provides evidence of suppression of tumor growth. Such anti-MHC-I mAb that block inhibitory KIR/HLA interactions may prove useful for tumor immunotherapy.

PubMed: 41333432
DOI: 10.21203/rs.3.rs-7133881/v1

実験手法

ELECTRON MICROSCOPY (2.67 Å)