Immunological Synapses Are Versatile Structures Enabling Selective T Cell Polarization

Depoil, David; Zaru, Rossana; Guiraud, Martine; Chauveau, Anne; Harriague, Julie; Bismuth, Georges; Utzny, Clemens; Müller, Sabina; Valitutti, Salvatore

doi:10.1016/j.immuni.2004.12.010

Cited by 139 publications

(140 citation statements)

References 31 publications

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“…IS formation has also been examined in cases where a T-cell can interact with multiple APCs. Under these circumstances, the formation and stability of the IS depends on the relative strength of the TCR signal (Depoil et al, 2005). Perhaps this phenomenon accounts for the variability of cap formation and stability in our assay.…”

Section: Discussionmentioning

confidence: 91%

Dynamic Movement of the Calcium Sensor STIM1 and the Calcium Channel Orai1 in Activated T-Cells: Puncta and Distal Caps

Barr

Bernot

Srikanth

et al. 2008

MBoC

129

142

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The proteins STIM1 and Orai1 are the long sought components of the store-operated channels required in T-cell activation. However, little is known about the interaction of these proteins in T-cells after engagement of the T-cell receptor. We found that T-cell receptor engagement caused STIM1 and Orai1 to colocalize in puncta near the site of stimulation and accumulate in a dense structure on the opposite side of the T-cell. FRET measurements showed a close interaction between STIM1 and Orai1 both in the puncta and in the dense cap-like structure. The formation of cap-like structures did not entail rearrangement of the entire endoplasmic reticulum. Cap formation depended on TCR engagement and tyrosine phosphorylation, but not on channel activity or Ca 2؉ influx. These caps were very dynamic in T-cells activated by contact with superantigen pulsed B-cells and could move from the distal pole to an existing or a newly forming immunological synapse. One function of this cap may be to provide preassembled Ca 2؉ channel components to existing and newly forming immunological synapses. INTRODUCTIONT-cell activation in response to antigen induces and requires the elevation of intracellular Ca 2ϩ (Hogan et al., 2003;Quintana et al., 2005;Feske, 2007). T-cell receptor (TCR) engagement leads to activation of well-documented signal transduction pathways that cause a rapid release of Ca 2ϩ from the endoplasmic reticulum (ER; Samelson, 2002;Panyi et al., 2004;Gwack et al., 2007a). The depletion of Ca 2ϩ from this internal store then leads to the opening of ion channels in the plasma membrane (PM) allowing an influx of Ca 2ϩ from outside the cell. The store-operated channel responsible for Ca 2ϩ influx in T-cells is known as the Ca 2ϩ release-activated Ca 2ϩ (CRAC) channel, which has been studied by electrophysiological techniques for many years (Lewis, 2001;Prakriya and Lewis, 2003;Cahalan et al., 2007;Hewavitharana et al., 2007;Hogan and Rao, 2007;Putney, 2007a).Sustained elevation of cytosolic Ca 2ϩ is required for complete T-cell activation (Iezzi et al., 1998;Lewis, 2001;Hogan et al., 2003;Feske, 2007). High levels of intracellular Ca 2ϩ are necessary to maintain the interaction between a T-cell and antigen-presenting cell (APC) that leads to formation of the specialized contact surface known as the immunological synapse (IS). Increased Ca 2ϩ levels are also required for the activation of transcription factors. In particular, elevated Ca 2ϩ maintains prolonged nuclear accumulation of nuclear factor of activated T-cells (NFAT) by activating the phosphatase calcineurin that dephosphorylates NFAT, allowing it to translocate to the nucleus and activate genes such as IL2 (Hogan et al., 2003;Macian, 2005). Several hours of Ca 2ϩ influx are required to complete the T-cell activation program, which involves expression of a large number of activation-associated genes (Lewis, 2001;Macian et al., 2002;Hogan et al., 2003).Although sustained Ca 2ϩ influx in T-cells has been studied for decades, the proteins involved have only been ident...

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Section: Discussionmentioning

confidence: 91%

Dynamic Movement of the Calcium Sensor STIM1 and the Calcium Channel Orai1 in Activated T-Cells: Puncta and Distal Caps

Barr

Bernot

Srikanth

et al. 2008

MBoC

129

142

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“…The observation that polarized mast cell degranulation requires local signalling and cytoskeletal rearrangement rather than the whole re-polarization of the cell is in agreement with previous data showing that an extension of microtubules is sufficient to guide granules to plasma membrane 45 . Second, they are apparently poorly motile and form relatively loose synaptic contacts with antibody-targeted cells when compared with T-cell synapses 49,50 . Thus, differently from T cells that undergo a complete reprogramming of their motility and polarization behaviour, mast cells release granules at the site of FcR triggering without profound changes in their motility.…”

Section: Discussionmentioning

confidence: 99%

Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence

et al. 2015

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Mast cells are tissue-resident immune cells that play a key role in inflammation and allergy. Here we show that interaction of mast cells with antibody-targeted cells induces the polarized exocytosis of their granules resulting in a sustained exposure of effector enzymes, such as tryptase and chymase, at the cell-cell contact site. This previously unidentified mast cell effector mechanism, which we name the antibody-dependent degranulatory synapse (ADDS), is triggered by both IgE-and IgG-targeted cells. ADDSs take place within an area of cortical actin cytoskeleton clearance in the absence of microtubule organizing centre and Golgi apparatus repositioning towards the stimulating cell. Remarkably, IgG-mediated degranulatory synapses also occur upon contact with opsonized Toxoplasma gondii tachyzoites resulting in tryptase-dependent parasite death. Our results broaden current views of mast cell degranulation by revealing that human mast cells form degranulatory synapses with antibody-targeted cells and pathogens for dedicated secretion and defence.

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“…6C. Most T cells that had partial contact with anti-CD3 rings showed focal clustering of PKC-colocalized with the MTOC at their points of contact with the activation site, as shown in (36), and they can also rapidly change the direction of polarization when a nearby stronger stimulus is detected (37). It is possible that semimotile T cells making only partial contact with annular activation sites may be in the process of continuously repolarizing their TCRs and signaling machinery around the annulus of ligand, seeking a focus of maximal stimulus.…”

Section: Modulation Of T Cell Responses By Altering Surface Ligand Pamentioning

confidence: 96%

Immunological synapse arrays: Patterned protein surfaces that modulate immunological synapse structure formation in T cells

Doh¹,

Irvine

2006

Proc. Natl. Acad. Sci. U.S.A.

162

157

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Immunological Synapses Are Versatile Structures Enabling Selective T Cell Polarization

Cited by 139 publications

References 31 publications

Dynamic Movement of the Calcium Sensor STIM1 and the Calcium Channel Orai1 in Activated T-Cells: Puncta and Distal Caps

Dynamic Movement of the Calcium Sensor STIM1 and the Calcium Channel Orai1 in Activated T-Cells: Puncta and Distal Caps

Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence

Immunological synapse arrays: Patterned protein surfaces that modulate immunological synapse structure formation in T cells

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