Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Immune synapses cannot function without ZAP-70


Img.1: Schematic model of the immune synapse:
* an inner "ring of receptors and signaling molecules.
* an outer "ring" with adhesion molecules.

Communication within the immune system

A familial form of severe combined immune deficiency (SCID) is caused by anomalies of an enzyme called ZAP-70. If ZAP-70 is lacking or does not work, the T-cells, which play a key role in the mechanisms of immune defense, are no longer functional. Affected children therefore catch infections as soon as they are exposed to pathogenic microorganisms. The only treatment at present is bone marrow transplantation.

INSERM research scientists at the Institut Curie have recently described the essential role of ZAP-70 in the communication between immune cells, in the October 2002 issue of Immunity.

Considerable progress has been made in recent years in clarifying the subtleties of communication between cells of the immune system. Numerous signaling molecules have been identified and subtle mechanisms unraveled. A succession of studies since 1998 has shown that the interaction between cells of the immune system is highly organized through narrow junctions called synapses, like their counterparts between neurons. These fundamental advances in the study of cell communication are crucially important for better understanding and improved treatment of immune system dysfunction.

D4 cells no longer respond

Various characteristics observed in young patients suffering from this form of severe immune deficiency prompted Claire Hivroz and her group to study the role of ZAP-70 and its involvement in the mechanisms of signal transmission between cells of the immune system.

These young patients, for instance, have normal counts of CD4+ T-cells — immune cells that activate killer T-cells and antibody-producing B-cells – yet do not secrete antibodies in response to an infection.

In fact, CD4+ T-cells do not respond to stimulation by antigen-presenting cells (APCs) (see Img. 1). Normally, the interaction at the synapse between a T-cell and an APC leads to the activation of a series of enzymes, including ZAP-70, and culminates in the secretion of molecules that induce B-cells to synthesize antibodies.

Synapse organization involves a cascade of events

Scientists at the Institut Curie are investigating the highly disruptive consequences of the absence of ZAP-70 at the synapse. When ZAP-70 is normal, molecular “rings” are formed at the intercellular contact or immune synapse between two cells. One of these rings comprises receptors, co-receptors and signaling molecules, which ensure the connection between the signal received from outside the cell and the triggering of a program of switching on genes in the T-cell nucleus.

Another ring (outside the first) is composed principally of adhesion proteins and maintains the physical contact between the two cells (see Img 1).

At the same time, within the T-cell, the cytoskeleton orchestrates the movement of surface proteins at this cell junction.

The microtubules move and form “tracks” which guide intracellular vesicles containing signaling molecules to the synapse.

All these events, which lead to the formation of a functional synapse, unfold according to a precise scenario in time and space. There are, however, variations in the type of molecules recruited to the rings and in the way the cytoskeleton is organized depending on the cell pair involved: T-cell / B-cell; T-cell dendritic cell; B-cell / dendritic cell; killer T-cell / target cell, etc.

ZAP-70 is an indispensable link in signal transmission

Research scientists at the Institut Curie have chosen to take a B-cell as an antigen-presenting cell and to study its interaction with a T-cell. Using videomicroscopy, they have compared ZAP-70-expressing cells with cells in which ZAP-70 is either lacking or altered.

They have shown that ZAP-70 is essential for the correct unfolding of the events that occur within the T-cell. ZAP-70 participates in guiding the signaling molecules towards the immune synapse. The absence of ZAP-70 does not disrupt the general organization of the rings, that is the gathering of the membrane molecules and the positioning of surface molecules at the synapse. In contrast, intracellular events are highly dependent on its presence, and if ZAP-70 is absent the microtubule network does not orientate correctly and some signaling molecules do not accumulate in the synaptic zone.

Apart from a better understanding of the molecular basis of this immune deficiency, this work has more accurately identified the events occurring when immune cells touch and communicate. ZAP-70 is an indispensable link in the cascade of signals directed towards the nucleus, which culminate in activation of the T-cell.

Institut Curie researchers are now seeking to understand how ZAP-70 controls the reorientation of the microtubules towards the synapse and to analyze the role of the antigen-presenting cell in ring formation.


"In the immune synapse, ZAP-70 controls T-cell polarization and recruitment of signaling proteins but not formation of the synaptic pattern"

Nicolas Blanchard1, Vincenzo Di Bartolo2 and Claire Hivroz1
Immunity, vol. 17, 389-399, October 2002

1Inserm U520, Institut Curie
2Unité d’Imunologie moléculaire, Institut Pasteur

Press contacts
Institut Curie
Press Relations
Catherine Goupillon
Phone 01 44 32 40 63

Cécile Charré
Phone 01 44 32 40 51
Fax 01 44 32 41 67

Inserm Press Center
Nathalie Christophe
Phone 01 44 23 60 85
Séverine Ciancia
Phone 01 44 23 60 86

Catherine Goupillon | Institut Curie
Further information:

More articles from Life Sciences:

nachricht Biologists unravel another mystery of what makes DNA go 'loopy'
16.03.2018 | Emory Health Sciences

nachricht Scientists map the portal to the cell's nucleus
16.03.2018 | Rockefeller University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

Im Focus: Radar for navigation support from autonomous flying drones

At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.

Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

International Virtual Reality Conference “IEEE VR 2018” comes to Reutlingen, Germany

08.03.2018 | Event News

Latest News

Wandering greenhouse gas

16.03.2018 | Earth Sciences

'Frequency combs' ID chemicals within the mid-infrared spectral region

16.03.2018 | Physics and Astronomy

Biologists unravel another mystery of what makes DNA go 'loopy'

16.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>