Figure 2.

T lymphocyte—antigen-presenting cells (APC) immune synapse (IS) and polarized secretion. Stages 0 and 1 are common for both Th and cytotoxic T lymphocytes (CTL) IS. After the initial scanning contact of TCR with pMHC on APC, Th effector T lymphocytes (upper panel) form mature IS with antigen-presenting B lymphocytes within several minutes. This IS lasts many hours during which de novo cytokine (i.e., IL-2, IFN-γ) production and secretion occur, which require continuous T-cell receptors (TCR) signaling. Primed effector CTL (lower panel) establish more transient, mature IS after scanning their target cells (i.e., a virus-infected cell), and deliver their lethal hits within a few minutes. Secretory lysosomes (lytic granules) are very rapidly transported (within very few minutes) towards the microtubule organization center (MTOC) (in the minus “–“ direction) and, almost simultaneously, the MTOC polarizes towards the central supramolecular activation complex (cSMAC) of the IS, an F-actin poor area that constitutes a secretory domain. MTOC translocation to the IS appears to be dependent on dynein anchored to the Adhesion and Degranulation Promoting Adapter Protein (ADAP) at the peripheral SMAC (pSMAC), which pulls MTOC in the minus direction. In both types of IS (lower zoom panel), the initial F-actin reorganization in the cell-to-cell contact area, followed by a decrease in F-actin at the cSMAC and an accumulation at the distal SMAC (dSMAC) appears to be involved in granule secretion. In stage 3, MVB fusion with the plasma membrane occurs in both types of IS and leads to TCR-containing exosome polarized secretion at the IS. The exosomes released in Th IS contain proapoptotic FasL and Apo2L and can induce target cell death or Th cell death (AICD). TCR–containing shedding microvesicles have been described in Th IS.