Lymphocyte Cell Biology - CNRS URA 1961  


  HEADDr Andrés ALCOVER / aalcover@pasteur.fr
  MEMBERSChercheurs statutaires : Dr Vincenzo Di BARTOLO / Dr Maria-Isabel THOULOUZE
Chercheurs post-doctoraux : Dr Rémi LASSERRE / Dr Stéphanie CHARRIN
Etudiants en thèse : Ana-Monica PAIS-CORREIA / Valentina ROBBIATI
Technicienne : Céline CUCHE
Secrétaire : Cécile ROUX


  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.

Role of the actin cytoskeleton in the formation of immunological synapses and in T cell activation

We previously showed 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). By specifically depleting ezrin from T cells, using siRNA, we recently unravelled an important role for ezrin in the modulation of early and late T cell activation events. We are currently disecting the mechanism by which ezrin tunes up T cell signaling.

Immunological synapse: a target for lymphotropic retroviruses.

We previously showed that intracellular endosomal trafficking is a key mechanism for molecular transport to the immunological synapse (Das et al, Immunity, 2004). Moreover, we showed that human immunodeficiency virus (HIV-1), by means of its protein Nef, targets this process, impairing the transport of the T cell receptor and of the protein tyrosine kinase Lck through endosomes to the synapse. This perturbs the formation and function of immunological synapses formed by infected T cells (Thoulouze et al, Immunity, 2006). Our recent data show that this mechanism targets only some particular molecules that traffic through endosomes leaving other molecules unperturbed. This underlines the importance and complexity of vesicle trafficking in the generation of immunological synapses and in T lymphocyte activation.

Keywords: Immunological synapse, T cell activation, T cell signaling, polarization, virological synapse, HIV, AIDS, intracellular traffic, endosomes

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  Publications

- Das V., Nal B., Dujeancourt A., Thoulouze M. I., Galli T., Roux P., Dautry-Varsat A., Alcover A. 2004. Activation-induced polarized recycling targets T cell receptors to the immunological synapse. Involvement of SNARE complexes. Immunity. 20: 577-588. PMID: 15142526

- Thoulouze M. I., Sol-Foulon N., Blanchet F., Dautry-Varsat A., Schwartz O., Alcover A. 2006. Human immunodefficiency virus (HIV-1) impairs the formation of the immunological synapse. Immunity. 24 :547-561. PMID: 16713973

- Charrin S., Alcover A. 2006. Role of ERM (ezrin-radixin-moesin) proteins in T lymphocyte polarization, immune synapse formation and in T cell receptor-mediated signaling. Front. Biosci. 11 : 1987-1997. PMID: 16368573

- Schwartz O., Alcover A., Fackler O. T. 2007. Modulation of the immunological synapse : a key to HIV-1 pathogenesis ? Nature Revs Immunol. 7 : 310-317. PMID: 17380160

- Sol-Foulon N., Sourisseau, M., Porrot, F., Thoulouze, M. I., Trouillet, C., Nobile, C., Blanchet, F., Di Bartolo, V., Noraz, N., Taylor, N., Alcover, A., Hivroz, C., Schwartz, O. 2007. ZAP-70 kinase regulates HIV cell-to-cell spread and virological synapse formation. EMBO J. 26 : 512-526. PMID: 17215865





Activity Reports 2007 - Institut Pasteur
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