g(m1)-ganglioside and Wiskott-Aldrich-Syndrome

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.

Topics: Calcium; CD28 Antigens; Cell Division; Cells, Cultured; G(M1) Ganglioside; Humans; Lymphocyte Activation; Membrane Microdomains; Proteins; Receptors, Antigen, T-Cell; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein