The Wiskott-Aldrich Syndrome Protein Contributes to the Assembly of the LFA-1 Nanocluster Belt at the Lytic Synapse

Cell Rep. 2018 Jan 23;22(4):979-991. doi: 10.1016/j.celrep.2017.12.088. Epub 2018 Jan 28.


T lymphocyte cytotoxicity relies on a synaptic ring of lymphocyte function-associated antigen 1 (LFA-1), which permits polarized delivery of lytic granules. How LFA-1 organization is controlled by underlying actin cytoskeleton dynamics is poorly understood. Here, we explored the contribution of the actin cytoskeleton regulator WASP to the topography of LFA-1 using a combination of microscopy modalities. We uncover that the reduced cytotoxicity of Wiskott-Aldrich syndrome patient-derived CD8+ T lymphocytes lacking WASP is associated with reduced LFA-1 activation, unstable synapse, and delayed lethal hit. At the nanometric scale, WASP constrains high-affinity LFA-1 into dense nanoclusters located in actin meshwork interstices. At the cellular scale, WASP is required for the assembly of a radial belt composed of hundreds of LFA-1 nanoclusters and for lytic granule docking within this belt. Our study unravels the nanoscale topography of LFA-1 at the lytic synapse and identifies WASP as a molecule controlling individual LFA-1 cluster density and LFA-1 nanocluster belt integrity.

Keywords: LFA-1; Wiskott-Aldrich syndrome protein; actin cytoskeleton; cytotoxic T lymphocytes; immunological synapse; lytic granules; super-resolution microscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Humans
  • Lymphocyte Function-Associated Antigen-1 / genetics*
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Synapses / metabolism*
  • Wiskott-Aldrich Syndrome Protein / genetics*


  • Lymphocyte Function-Associated Antigen-1
  • Wiskott-Aldrich Syndrome Protein