LAG3 facilitates MHC Ⅱ trogocytosis with assistance of the ER-PM junction
Zibin Wang1
Jing Wang2
Wene Zhao1
Wen Liu3
1.Analysis and Test Center,Nanjing Medical University,Nanjing,Jiangsu 211166,China2.Department of Reproductive Medicine,Zhongda Hospital,School of Medicine,Southeast University,Nanjing,Jiangsu 210009,China3.School of Life Sciences,Nanjing University,Nanjing,Jiangsu 210023,China
摘要：Dear Editor,
Lymphocyte activation gene 3 (LAG3),the third established target for immune checkpoint blockade therapy,suppresses T cell function by binding to major histocompatibility complex class Ⅱ (MHC Ⅱ).Despite its significant therapeutic potential in cancer immunotherapy and the substantial attention it has received from academia and industry,the molecular mechanisms of LAG3-mediated immunosuppression remain poorly understood,primarily because of its unique ligand-binding characteristics and intracellular domains[1]. Recent studies have advanced our understanding of LAG3 function. Maruhashi et al[2]have demonstrated that stable peptide-MHC Ⅱ,rather than fibrinogen-like protein (FGL1),serves as the functional ligand for LAG3-mediated T cell suppression in both autoimmunity and anti-cancer immunity. Jiang et al[3]have revealed the molecular mechanism by which LAG3 is activated by MHC Ⅱ-mediated ligand engagement,with ubiquitination activating LAG3 by releasing its cytoplasmic tail (CT)from the membrane. Notably,LAG3 associates with the T cell receptor (TCR)-CD3 complex and traffics to the immunological synapse (IS),where clustering of its CT through a phase separation mechanism disrupts interactions between coreceptors CD4/CD8 and the kinase Lck,thereby impairing TCR signaling and reducing T cell activation[4]. These studies have deepened our understanding of LAG3's immuno-modulatory mechanisms and highlighted the need to elucidate the molecular mechanisms underlying the biological function of the LAG3-MHC Ⅱ interaction in a true cell-cell contact system.
机标关键词：withassistancefacilitatesjunctiontrogocytosis
分类号：R392.1(医学免疫学)
论文发表日期：2026-01-30
在线出版日期：2026-01-29（本平台首次上网日期，不代表文献的发表时间）
页数：4( 89-92 )