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The magnitude of LFA-1/ICAM-1 forces fine-tune TCR-triggered T cell activation

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)/intercellula...

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Detalles Bibliográficos
Autores principales: Ma, Victor Pui-Yan, Hu, Yuesong, Kellner, Anna V., Brockman, Joshua M., Velusamy, Arventh, Blanchard, Aaron T., Evavold, Brian D., Alon, Ronen, Salaita, Khalid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880789/
https://www.ncbi.nlm.nih.gov/pubmed/35213231
http://dx.doi.org/10.1126/sciadv.abg4485
Descripción
Sumario: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.