Tuning immune responses: diversity and adaptation of the immunological synapse

Abstract

The onset and regulation of a specific immune response results from communication between T cells and antigen-presenting cells (APCs), which form molecular interactions at the site of cell-cell contact--and this is known as the immunological synapse. Initially, the immunological synapse was viewed as a stereotypical adhesion and signalling device with a defined molecular structure and signalling processes. However, as we discuss here, T-cell-APC interactions comprise a diverse range of contact modes and distinct molecular arrangements. These diverse interaction modes might define a molecular code, in which the differences in timing, spacing and molecular composition of the signalling platform determine the outcome of T-cell-APC interactions.

Synthetic Multivalent Ligands as Probes of Signal Transduction

“…Its structure is influenced by the type of APC involved, the type and activation state of the T cell, the duration of the T cell-APC interaction, and the local physiological environment in which it forms. [74] Powerful new imaging methods have been used to visualize immune synapses formed in vitro and in vivo; these studies reveal that dynamic changes in protein localization and organization can occur. At a molecular level, the role protein organization within the synapse not yet been established: It is not known whether the observed organization of the receptors on the T cell influences signaling.…”

How stem cells speak with host immune cells in inflammatory brain diseases

“…Stem cell signaling takes place through different pathways that involve networks of interacting molecules transmitting information between the graft and the host. This exchange of signals entails either cell-to-cell contacts (juxtacrine) or gradients formed by soluble factors (paracrine) (Friedl et al, 2005) which also circulate in blood and body fluids and act in a regional or systemic manner (endocrine). Stem cell signaling may also involve the newly recognized release of extracellular membrane vesicles (EVs) (Kalra et al, 2012;Mathivanan et al, 2010;Thery et al, 2002).…”

Calcium dependence of T cell proliferation following focal stimulation

“…In the early phase of IS forming, Ca 2+ signaling is initiated, and many signaling molecules such as CD3f, the lymphocyte-specific protein tyrosine kinase (LCK) and the f-chain-associated protein kinase of 70 kDa (ZAP70) are recruited to the signaling platform at the IS and determine the outcome of the T cell-APC interaction. In addition, costimulatory molecules move to the contact zone in the early phase of IS forming, which are required to produce a sufficient T cell response [3]. The most widely investigated receptor couple is the CD28 molecule including its interacting partner molecules of the B7 family [4,5].…”

“…One of the early signaling cascades induced by the engagement of TCR at the IS is the tyrosine phosphorylation of phospholipase C-c, which hydrolyzes phosphatidylinositol 4,5 bisphosphate to inositol 1,4,5 trisphosphate (InsP 3 ) and diacylglycerol [6]. InsP 3 releases Ca 2+ from internal Ca 2+ stores and the Ca 2+ store depletion activates store-operated Ca 2+ channels called Ca 2+ release-activated Ca 2+ (CRAC)/ORAI channels in T cells [7,8].…”

“…InsP 3 releases Ca 2+ from internal Ca 2+ stores and the Ca 2+ store depletion activates store-operated Ca 2+ channels called Ca 2+ release-activated Ca 2+ (CRAC)/ORAI channels in T cells [7,8]. There is no doubt that Ca 2+ signaling is required for clonal expansion (proliferation) of T cells as well as for the generation and activation of effector cells [9][10][11].…”