Nanoscale kinetic segregation of TCR and CD45 in engaged microvilli facilitates early T cell activation

Yair Razvag, Yair Neve-Oz, Julia Sajman, Meital Reches, Eilon Sherman

Research output: Contribution to journalArticlepeer-review

Abstract

T cells have a central function in mounting immune responses. However, mechanisms of their early activation by cognate antigens remain incompletely understood. Here we use live-cell multi-colour single-molecule localization microscopy to study the dynamic separation between TCRs and CD45 glycoprotein phosphatases in early cell contacts under TCR-activating and non-activating conditions. Using atomic force microscopy, we identify these cell contacts with engaged microvilli and characterize their morphology, rigidity and dynamics. Physical modelling and simulations of the imaged cell interfaces quantitatively capture the TCR-CD45 separation. Surprisingly, TCR phosphorylation negatively correlates with TCR-CD45 separation. These data support a refined kinetic-segregation model. First, kinetic-segregation occurs within seconds from TCR activation in engaged microvilli. Second, TCRs should be segregated, yet not removed too far, from CD45 for their optimal and localized activation within clusters. Our combined imaging and computational approach prove an important tool in the study of dynamic protein organization in cell interfaces.

Original languageAmerican English
Article number732
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2018

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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