Vesicular Trafficking to the Immune Synapse: How to Assemble Receptor-Tailored Pathways from a Basic Building Set

Onnis, Anna; Finetti, Francesca; Baldari, Cosima T.

doi:10.3389/fimmu.2016.00050

Cited by 32 publications

(34 citation statements)

References 112 publications

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“…It is the opinion of the authors that the dynamic nature of TCR surface expression makes it likely that dual TCR T cells are functionally dual specific. In support of this view, it has been suggested that TCRs recycled from the cell surface can serve as an intracellular store of functional TCR that can be rapidly directed to the immune synapse after ligand engagement of surface TCRs (96). In T cells with two rearranged TCR a-chains, this intracellular store contains surface-excluded TCR a-chains that could be mobilized, overcoming phenotypic allelic exclusion and allowing the cell to be activated in response to this second specificity (Fig.…”

Section: Evolutionary Pressurementioning

confidence: 94%

Dual TCR T Cells: Identity Crisis or Multitaskers?

Schuldt

Binstadt

2019

The Journal of Immunology

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Dual TCR T cells are a common and natural product of TCR gene rearrangement and thymocyte development. As much as one third of the T cell population may have the capability to express two different TCR specificities on the cell surface. This discovery provoked a reconsideration of the classic model of thymic selection. Many potential roles for dual TCR T cells have since been hypothesized, including posing an autoimmune hazard, dominating alloreactive T cell responses, inducing allergy, and expanding the TCR repertoire to improve protective immunity. Yet, since the initial wave of publications following the discovery of dual TCR T cells, research in the area has slowed. In this study, we aim to provide a brief but comprehensive history of dual TCR T cell research, re-evaluate past observations in the context of current knowledge of the immune system, and identify key issues for future study.

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Section: Evolutionary Pressurementioning

confidence: 94%

Dual TCR T Cells: Identity Crisis or Multitaskers?

Schuldt

Binstadt

2019

The Journal of Immunology

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“…As previously stated, IS formation is dependent on actin cytoskeleton dynamics in two ways: first, by promoting T cell mobility necessary for APC scanning and second, by mediating the spatiotemporal organisation of IS components at the contact site, which conditions subsequent signalling cascade (Roy & Burkhardt, ). In addition, intracellular vesicular trafficking is a central player of IS assembly and maintenance and is required for T cell activation (Alcover & Alarcon, ; Onnis, Finetti, & Baldari, ). Considering the impact of Shigella on these two critical pathways presented above, we thus investigated the formation of ISs upon T cell infection.…”

Section: Resultsmentioning

confidence: 99%

Shigellaimpairs human T lymphocyte responsiveness by hijacking actin cytoskeleton dynamics and T cell receptor vesicular trafficking

Samassa

Ferrari

Husson

et al. 2020

Cellular Microbiology

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Strategies employed by pathogenic enteric bacteria, such as Shigella, to subvert the host adaptive immunity are not well defined. Impairment of T lymphocyte chemotaxis by blockage of polarised edge formation has been reported upon Shigella infection. However, the functional impact of Shigella on T lymphocytes remains to be determined. Here, we show that Shigella modulates CD4+ T cell F‐actin dynamics and increases cell cortical stiffness. The scanning ability of T lymphocytes when encountering antigen‐presenting cells (APC) is subsequently impaired resulting in decreased cell–cell contacts (or conjugates) between the two cell types, as compared with non‐infected T cells. In addition, the few conjugates established between the invaded T cells and APCs display no polarised delivery and accumulation of the T cell receptor to the contact zone characterising canonical immunological synapses. This is most likely due to the targeting of intracellular vesicular trafficking by the bacterial type III secretion system (T3SS) effectors IpaJ and VirA. The collective impact of these cellular reshapings by Shigella eventually results in T cell activation dampening. Altogether, these results highlight the combined action of T3SS effectors leading to T cell defects upon Shigella infection.

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“…Since these early studies, it has become evident that the immune synapse is an active zone for directional exocytosis, endocytosis, receptor recycling and more generally vesicular traffic [8][9][10][11]]. Yet, how vesicular trafficking is involved in T cell activation is still only partially understood.…”

Section: Discussionmentioning

confidence: 99%

Purification of LAT-Containing Membranes from Resting and Activated T Lymphocytes

et al. 2017

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In T lymphocytes, the immune synapse is an active zone of vesicular traffic. Directional transport of vesicular receptors and signaling molecules from or to the immune synapse has been shown to play an important role in T-cell receptor (TCR) signal transduction. However, how vesicular trafficking is regulating the activation of T cells is still a burning question, and the characterization of these intracellular compartments remains the first step to understand this process. We describe herein a protocol, which combines a separation of membranes on flotation gradient with an affinity purification of Strep-tagged fusion transmembrane proteins with Strep-Tactin resin, allowing the purification of membranes containing the Strep-tagged molecule of interest. By keeping the membranes intact, this protocol leads to the purification of molecules physically associated with the Strep-tagged protein as well as of molecules present in the same membrane compartment: transmembrane proteins, proteins strongly associated with the membranes, and luminal proteins. The example shown herein is the purification of membrane compartment prepared from T lymphocytes expressing LAT fused to a Strep-tag.

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Vesicular Trafficking to the Immune Synapse: How to Assemble Receptor-Tailored Pathways from a Basic Building Set

Cited by 32 publications

References 112 publications

Dual TCR T Cells: Identity Crisis or Multitaskers?

Dual TCR T Cells: Identity Crisis or Multitaskers?

Shigellaimpairs human T lymphocyte responsiveness by hijacking actin cytoskeleton dynamics and T cell receptor vesicular trafficking

Purification of LAT-Containing Membranes from Resting and Activated T Lymphocytes

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