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Rac 1 and 2, two proteins essential to triggering of the immune response

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23.08.2004

When a dendritic cell meets a T cell… The dendritic cell and its “arms” can be seen on the left of the images. On the right is a smaller T cell. In the first image, the dendritic cell reaches out in search of a T cell. In the second image, it finds a T cell and extends its arms towards it. In the third image, the dendritic cell entraps the T cell. © F. Benvenuti/Institut Curie


In this dendritic cell, the proteins Rac 1 and 2 are inactive. The dendritic cell is "unaware" of the presence of the T cell. © F. Benvenuti/Institut Curie

The dendritic cells act as the body’s sentries, standing guard around the clock. As soon as they detect a potential enemy, they alert the T cells, whose role is to defend the body.

At the Institut Curie, CNRS researchers in an Inserm laboratory have filmed the encounter of dendritic cells and T cells. They have shown that this "rendez-vous", which is indispensable for the activation of the immune system, cannot take place in the absence of the proteins Rac 1 and 2. Published in the August 20, 2004 issue of Science, this discovery yields new information on the immune system and could in time pave the way for advances in immunotherapy.

Our immune system is on call round the clock. Whenever a foreign body intrudes (virus, bacterium…), or even in response to the anarchic proliferation of the body’s own cells (cancer), the immune system sounds the alarm.

Dendritic cells are the "sentries" responsible for detecting the presence of an intruder in our body. When they locate a potentially dangerous cell, they partially ingest it and isolate a characteristic fragment, an antigen(1). Bearing this fragment they then migrate to the lymph nodes, where the T cells are to be found. The dendritic cells present the antigen to T cells, thus enabling them to recognize the enemy, which they must eliminate. Once informed, T cells launch a targeted offensive to rid the body of bacteria, tumor cells or virus-infected cells. At the Institut Curie, Sebastian Amigorena(2) and his team are studying how the body’s sentries identify the antigen and then present it to the T cells.

The dendritic cell stretches out its arms…

To observe the in vivo meeting between dendritic cells and T cells in the lymph nodes, Sebastian Amigorena and colleagues, in partnership with Luc Fetler(3), have used the highly sophisticated technique of two-photon microscopy (see box). This is the first time in Europe that two-photon microscopy has been utilized to follow the triggering of immune responses in vivo, in intact organs.

Rather like starfish, dendritic cells have several "arms", formed by membrane extensions. Once they reach the lymph nodes, the dendritic cells stretch out these arms in their search for T cells(4).

…and entraps the T cell

When a T cell is found, the dendritic cell’s arms stretch towards it by extension of the cell membrane and "engulf" it. The Institut Curie scientists noted that this "engulfment", which is essential to effective triggering of an immune response, cannot occur without the presence of proteins Rac 1 and 2(5). These two proteins control the extension of the dendritic cell membrane when the T cell is contacted. When Rac 1 and 2 are inactivated, the meeting between the T cells and the dendritic cells does not happen and as a result the immune response is not triggered.

This discovery should lead to optimization of one of the promising approaches to cancer treatment – immunotherapy, in which the immune system is used to destroy tumor cells. By measuring the expression and activation state of Rac 1 and 2, it may be possible to assess, and if necessary enhance, the efficacy of dendritic cells in initiating the immune response.

(1)Antigen: a foreign or abnormal agent specific to a cell which triggers an immune reaction. In general it is a protein fragment.
(2)Sebastian Amigorena is a CNRS Director of Research and heads Inserm unit 365 “Interferons and cytokines”.
(3)As a member of the "Physics of the cytoskeleton and membrane functions" team (UMR 168 CNRS/IC "physicochimie Curie") directed by François Amblard, Luc Felter is participating in the development of two-photon microscopy.
(4)Using their membrane extensions, the dendritic cells inspect a region four times greater than their own surface area.
(5)Rac 1 and 2 belong to a large family of proteins, the Rho-GTPases, which are known to play a part in the formation of the cytoskeleton. This network of microfilaments, which forms the skeleton of cells, is responsible for their shape, rigidity and internal organization.

Catherine Goupillon | Source: alphagalileo

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