Related Experiment Video
Updated: Jan 7, 2026

Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells
Published on: March 28, 2025
Lipid-Gated "Phosphorylation Code" for TCR Graded Signaling and T-cell exhaustion
Hui Chen1, Jizhong Lou1, Wei Chen2
1State Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Abstract:
The TCR/CD3s complex translates antigenic cues into graded immune responses. Xu and colleagues (Molecular Cell, 2025) revealed a lipid-electrostatic mechanism that governs sequential phosphorylation of the CD3ζ chain. Using NMR in a membrane-mimetic system, they uncovered a gradient of membrane insertion across its ITAMs, establishing a structural basis for tunable signaling. Under chronic stimulation, ATP depletion preferentially impairs distal ITAM phosphorylation, revealing an intrinsic energy-sensitive pathway driving T cell exhaustion. These findings provide a compelling model for TCR regulation and suggest strategies to enhance immunotherapy via CD3ζ engineering or metabolic restoration.
More Related Videos
Related Concept Videos
Amplifying Signals via Enzymatic Cascade
GPCR Desensitization
T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
TGF - β Signaling Pathway
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...

