Lymphocyte Cell Biology - CNRS URA1961  


  HEADALCOVER Andrés / aalcover@pasteur.fr
  MEMBERSDr CHARRIN Stéphanie / Dr DI BARTOLO Vincenzo / Dr LASSERRE Rémi
PAIS-CORREIA Ana Monica / ROBBIATI Valentina / Dr THOULOUZE Maria Isabel


  Annual Report

Following antigen recognition, T cells polarize towards antigen presenting cells concentrating T cell receptors, adhesion molecules, signaling effectors and cytoskeleton components at the antigen presenting cell contact site. This cellular contact was named the immunological synapse, since it ensures the communication between the T cell and the antigen presenting cell.

We investigate the molecular mechanisms that generate immunological synapses and their role in T cell activation. We also study how lymphotropic retroviruses hijack the mechanisms that generate immunological synapses to modulate T cell responses and to spread more efficiently from cell to cell.

Immunological synapse: role of the actin cytoskeleton

We have previously shown that ezrin, a protein that links the membrane with the actin cytoskeleton, is involved in the formation of the immunological synapse and in T cell activation (Roumier et al., Immunity, 2001). More recently, by specifically depleting ezrin from T cells, using siRNA approaches, we investigated how ezrin differentially regulates early and late T cell signaling events, providing evidence for an important role of ezrin in tuning up T cell activation.

Intracellular vesicle trafficking during the formation of the immunological synapse. Modulation by HIV-1

We have previously shown that intracellular endosomal trafficking is a key molecular transport mechanism to generate immunological synapses (Das et al, Immunity, 2004). We have recently shown that the human immunodeficiency virus (HIV-1) targets this transport process, by means of the viral protein Nef, and impedes the vesicular transport of T cell receptors and of the protein tyrosine kinase Lck, thus impairing the formation and function of immunological synapses (Thoulouze et al, Immunity, 2006). Our data unravel a novel mechanism by which HIV-1 modulates T lymphocyte activation, and underlines the importance of intracellular vesicular traffic in the generation of the immunological synapse.

alcover.jpg

Lymphocyte T infecté par HIV-1 présentant une accumulation de la tyrosine kinase Lck (rouge) dans le compartiment endosomial marqué par le récepteur à la trasferrine (rouge)



  Publications

Publications 2006 of the unit on Pasteur's references database




Activity Reports 2006 - Institut Pasteur
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