Resolving protein interactions and organization downstream the T cell antigen receptor using single-molecule localization microscopy: A review

Eilon Sherman*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations


Signal transduction is mediated by heterogeneous and dynamic protein complexes. Such complexes play a critical role in diverse cell functions, with the important example of T cell activation. Biochemical studies of signalling complexes and their imaging by diffraction limited microscopy have resulted in an intricate network of interactions downstream the T cell antigen receptor (TCR). However, in spite of their crucial roles in T cell activation, much remains to be learned about these signalling complexes, including their heterogeneous contents and size distribution, their complex arrangements in the PM, and the molecular requirements for their formation. Here, we review how recent advancements in single molecule localization microscopy have helped to shed new light on the organization of signalling complexes in single molecule detail in intact T cells. From these studies emerges a picture where cells extensively employ hierarchical and dynamic patterns of nano-scale organization to control the local concentration of interacting molecular species. These patterns are suggested to play a critical role in cell decision making. The combination of SMLM with more traditional techniques is expected to continue and critically contribute to our understanding of multimolecular protein complexes and their significance to cell function.

Original languageAmerican English
Article number022002
JournalMethods and Applications in Fluorescence
Issue number2
StatePublished - Jun 2016

Bibliographical note

Funding Information:
The author would like to thank Zeiss, Harald Hess (HHMI, Janelia Farm) for providing the PALM software and Thorstan Wiegand (Helmholtz Centre for Environmental Research-UFZ) for providing us his point pattern analyses software. 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:
© 2016 IOP Publishing Ltd.


  • Photoactivated localization microscopy
  • Protein interaction
  • Second order statistics
  • Signaling complexes
  • Single molecule
  • Super resolution microscopy
  • T cell activation


Dive into the research topics of 'Resolving protein interactions and organization downstream the T cell antigen receptor using single-molecule localization microscopy: A review'. Together they form a unique fingerprint.

Cite this