The magnitude of LFA-1/ICAM-1 forces fine-tune TCR-triggered T cell activation.
Victor Pui-Yan MaYuesong HuAnna V KellnerJoshua M BrockmanArventh VelusamyAaron T BlanchardBrian D EvavoldRonen AlonKhalid SalaitaPublished in: Science advances (2022)
T cells defend against cancer and viral infections by rapidly scanning the surface of target cells seeking specific peptide antigens. This key process in adaptive immunity is sparked upon T cell receptor (TCR) binding of antigens within cell-cell junctions stabilized by integrin (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) complexes. A long-standing question in this area is whether the forces transmitted through the LFA-1/ICAM-1 complex tune T cell signaling. Here, we use spectrally encoded DNA tension probes to reveal the first maps of LFA-1 and TCR forces generated by the T cell cytoskeleton upon antigen recognition. DNA probes that control the magnitude of LFA-1 force show that F >12 pN potentiates antigen-dependent T cell activation by enhancing T cell-substrate engagement. LFA-1/ICAM-1 mechanical events with F >12 pN also enhance the discriminatory power of the TCR when presented with near cognate antigens. Overall, our results show that T cells integrate multiple channels of mechanical information through different ligand-receptor pairs to tune function.
Keyphrases
- single molecule
- regulatory t cells
- single cell
- dendritic cells
- small molecule
- circulating tumor
- cell therapy
- living cells
- induced apoptosis
- cell free
- high resolution
- sars cov
- air pollution
- social media
- squamous cell carcinoma
- cell cycle arrest
- mental health
- fluorescence imaging
- gene expression
- cell proliferation
- binding protein
- escherichia coli
- endoplasmic reticulum stress
- staphylococcus aureus
- bone marrow
- heat shock
- cell migration
- transcription factor
- oxidative stress
- biofilm formation
- signaling pathway
- childhood cancer
- mesenchymal stem cells
- pi k akt
- circulating tumor cells