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The T cell receptor displays lateral signal propagation involving non-engaged receptors.
Nieves, Daniel J; Pandzic, Elvis; Gunasinghe, Sachith D; Goyette, Jesse; Owen, Dylan M; Justin Gooding, J; Gaus, Katharina.
Afiliación
  • Nieves DJ; EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, Australia.
  • Pandzic E; Institute of Immunology and Immunotherapy, School of Mathematics, and Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham, UK. d.j.nieves@bham.ac.uk.
  • Gunasinghe SD; Katharina Gaus Light Microscopy Facility, Mark Wainwright Analytical Centre, University of New South Wales, Sydney, Australia.
  • Goyette J; EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, Australia.
  • Owen DM; EMBL Australia Node in Single Molecule Science, School of Medical Sciences and the ARC Centre of Excellence in Advanced Molecular Imaging, University of New South Wales, Sydney, Australia.
  • Justin Gooding J; Institute of Immunology and Immunotherapy, School of Mathematics, and Centre of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham, UK. d.j.nieves@bham.ac.uk.
  • Gaus K; School of Chemistry and Australian Centre for NanoMedicine, University of New South Wales, Sydney, Australia.
Nanoscale ; 14(9): 3513-3526, 2022 Mar 07.
Article en En | MEDLINE | ID: mdl-35171177
T cells are highly sensitive to low levels of antigen, but how this sensitivity is achieved is currently unknown. Here, we imaged proximal TCR-CD3 signal propagation with single molecule localization microscopy (SMLM) in T cells activated with nanoscale clusters of TCR stimuli. We observed the formation of large TCR-CD3 clusters that exceeded the area of the ligand clusters, and required multivalent interactions facilitated by TCR-CD3 phosphorylation for assembly. Within these clustered TCR-CD3 domains, TCR-CD3 signaling spread laterally for ∼500 nm, far beyond the activating site, via non-engaged receptors. Local receptor density determined the functional cooperativity between engaged and non-engaged receptors, but lateral signal propagation was not influenced by the genetic deletion of ZAP70. Taken together, our data demonstrates that clustered ligands induced the clustering of non-ligated TCR-CD3 into domains that cooperatively facilitate lateral signal propagation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Complejo Receptor-CD3 del Antígeno de Linfocito T Idioma: En Revista: Nanoscale Año: 2022 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos T / Complejo Receptor-CD3 del Antígeno de Linfocito T Idioma: En Revista: Nanoscale Año: 2022 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido