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 language | American English |
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Article number | 732 |
Journal | Nature Communications |
Volume | 9 |
Issue number | 1 |
DOIs | |
State | Published - 1 Dec 2018 |
Bibliographical note
Funding Information:This research was supported by Grant no. 321993 from the Marie Skłodowska-Curie actions of the European Commission, the Lejwa Fund, and Grants no. 1417/13 and no. 1937/13 from the Israeli Science Foundation.
Publisher Copyright:
© 2018 The Author(s).