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Molecular dynamics of lymphocyte interactions

Head : Salvatore Valitutti

Scientific objective :

The activation of T lymphocytes by antigenic ligands displayed on the surface of antigen presenting cells (APC) is the central event in developing an adaptive immune response. The interaction between T cells and APC during antigen recognition results in the formation of a specialized signaling area characterized by large scale molecular clustering and segregation of surface molecules and signaling components. This specialized area is named immunological synapse.
Our research team employs a combination of morphological, biochemical, molecular, functional and mathematical approaches to investigate cell-cell communication at the immunological synapse.

Our aims :

Our aims are:
- to provide a better definition of the molecular dynamics occurring at the immunological synapse during antigen recognition. We are specifically interested in the regulation of cellular polarity and in the remodeling of the actin cytoskeleton as key factors of immunological synapse assembly.
- to understand how the molecular dynamics occurring at the T cell-APC contact site influence T cell responses both in physiological and in pathological conditions.
In particular, we investigate :
1- how cancer cells perturb immunological synapse assembly,
2- how immunological synapse defects underlie certain primary immune deficiencies.

Main publications :

Bertrand F, Müller S, Roh KH, Laurent C, Dupré L, Valitutti S.
An initial and rapid step of lytic granule secretion precedes microtubule organizing center polarization at the cytotoxic T lymphocyte/target cell synapse.
Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):6073-8. Epub 2013 Mar 27.

Huang J, Brameshuber M, Zeng X, Xie J, Li Q, Chien Y, Valitutti S, Davis MM.
A single peptide-major histocompatibility complex ligand triggers digital cytokine secretion in CD4+ T cells

Malet-Engra G, Viaud J, Ysebaert L, Farcé M, Lafouresse F, Laurent G, Gaits-Iacovoni F, Scita G, Dupré L.
CIP4 controls CCL19-driven cell steering and chemotaxis in chronic lymphocytic leukemia.
Cancer Res
. 2013;73:3412-24.

Gaudenzio N, Laurent C, Valitutti S, Espinosa E.
Human mast cells drive memory CD4+ T cells toward an inflammatory IL-22+ phenotype.

J Allergy Clin Immunol
. 2013;131:1400-7.

Laurent C, Müller S, Do C, Al-Saati T, Allart S, Larocca LM, Hohaus S, Duchez S, Quillet-Mary A, Laurent G, Brousset P, Valitutti S.
Distribution, function, and prognostic value of cytotoxic T lymphocytes in follicular lymphoma: a 3-D tissue-imaging study


Gaudenzio N, Espagnolle N, Mars LT, Liblau R, Valitutti S, Espinosa E.
Cell-cell cooperation at the T helper cell/mast cell immunological synapse.
Blood., 2009 Dec 3;114(24):4979-88. Epub 2009 Oct 5.

Esquerré M, Tauzin B, Guiraud M, Müller S, Saoudi A, Valitutti S.

Human regulatory T cells inhibit polarization of T helper cells toward antigen-presenting cells via a TGF-beta-dependent mechanism.
Proc Natl Acad Sci U S A., 2008 Feb 19;105(7):2550-5. Epub 2008 Feb 11.

Last updated November 25, 2013

Version française

French version

Key words

Lymphocyte interactions
Anti-tumoral immunity
Immunological synapse
Confocal microscopy

Expected health effects

Our research activity is strongly dedicated to medically oriented questions. In particular, we are studying the immunological synapse as a key site of T cell activation modulation in the context of cancer. Our projects rely on primary cells and tissues isolated from patients through cooperation with local and international clinical centers. This research activity is expected to bring insight into crucial steps of the confrontation between T lymphocytes and tumor cells.
Centre de physiopathologie de Toulouse Purpan - CHU Purpan - BP 3028 31024 Toulouse Cedex 3
Inserm University of Toulouse Université Toulouse III - Paul Sabatier