The cytotoxic T lymphocyte immune synapse at a glance

Abstract

The immune synapse provides an important structure for communication with immune cells. Studies on immune synapses formed by cytotoxic T lymphocytes (CTLs) highlight the dynamic changes and specialised mechanisms required to facilitate focal signalling and polarised secretion in immune cells. In this Cell Science at a Glance article and the accompanying poster, we illustrate the different steps that reveal the specialised mechanisms used to focus secretion at the CTL immune synapse and allow CTLs to be such efficient and precise serial killers.

Imbalance of immunological synapse-kinapse states reflects tumor escape to immunity in glioblastoma

“…Activation of T cells requires physical contact with antigen-presenting cells (APCs) through the formation of the immunological synapse (IS) (5). After antigen recognition by CD3/T cell receptor (TCR) complexes, T cells become activated and arrange a particular intercellular and symmetric interface with target cells, establishing a characteristic bull's eye structure, involving the segregation and clustering of a group of molecules and organelles (6,7). Importantly, as initially described by Kupfer, T cells organize a CD3/TCR-rich central supramolecular activation cluster (cSMAC) surrounded by lymphocyte function-associated antigen (LFA-1) that segregates to the periphery of the interface forming a ring-shape cluster, named peripheral-SMAC (pSMAC), surrounded as well by a CD45-enriched distal SMAC (dSMAC) (8).…”

Transcellular communication at the immunological synapse: a vesicular traffic-mediated mutual exchange

“…Here, we will discuss the role of the IS in cell-to-cell communication in naïve T cells and focus on vesicular trafficking as the main regulator of this process. The polarized secretion of molecules at the IS by effector cells (that is, for example the lytic enzymes by cytotoxic T cells or immunomodulatory molecules by helper T cells) has been well characterized and described in other excellent reviews 1 , 13 , 14 .…”

Proteomic and functional analysis identifies galectin-1 as a novel regulatory component of the cytotoxic granule machinery

“…Exocytosis of lytic granules by cytotoxic cells is a Ca 2+ -dependent phenomenon that occurs in a very coordinated manner, initiated by the triggering of the TCR and culminating in target-directed release of their constituents. 2 To fully understand the molecular basis of CTL killing individual exploration of the biochemical and functional nature of purified cytotoxic granules is mandatory. Although some of the molecules are directly responsible for killing target cells, many others may be associated with positive or negative immune regulatory activities.…”

“…Immune-mediated elimination of intracellular microbes and cancer cells is accomplished by a complex lytic process orchestrated by CD8 + cytotoxic T lymphocytes (CTLs) and NK cells. 1 , 2 , 3 In response to antigen-specific recognition, biochemically defined signaling events triggered by T-cell receptor (TCR)/CD3 engagement and crosslinking of accessory molecules, leads to CD8 T-cell activation and differentiation. Subsequent TCR/CD3 stimulation results in release of a fraction of cytotoxic granules at the focal point of CTL/target cell contact, ensuring that a single CTL can kill multiple target cells in a specific fashion avoiding ‘off-target’ cytotoxic effects.…”

“…Subsequent TCR/CD3 stimulation results in release of a fraction of cytotoxic granules at the focal point of CTL/target cell contact, ensuring that a single CTL can kill multiple target cells in a specific fashion avoiding ‘off-target’ cytotoxic effects. 1 , 2 , 3 …”