Wiskott-Aldrich syndrome protein regulates lipid raft dynamics during immunological synapse formation

Abstract

Immunological synapse assembly relies on the clustering of lipid rafts and is required for optimal T cell activation. We demonstrate that the Wiskott-Aldrich syndrome protein (WASP) is recruited to lipid rafts immediately after TCR and CD28 triggering and is required for the movements of lipid rafts. T cells from Wiskott-Aldrich syndrome (WAS) patients, lacking WASP, proliferate poorly after TCR/CD28 activation and have impaired capacities to cluster the lipid raft marker GM1 and to upregulate GM1 cell surface expression. T cell proliferation and lipid raft clustering are restored by retroviral transfer of the WASP gene. These results demonstrate that WASP plays a central role in the movements of lipid rafts and identify a potential mechanism underlying the T cell defect affecting WAS patients.