Figure 1. Encounter between T cells and APC and initiation of IS formation. (1) T cells form random conjugates with APC mediated by the engagement of adhesion molecules such as LFA-1 and ICAM-1. (2) Following productive TCR engagement with peptide/MHC complexes the adhesion between the two cells increases and they form stable conjugates. (3) T cells change shape, stop migration, polarize secretory machinery towards the MAPC and start to rearrange the molecular components of the IS.

Figure 2. IS are dynamic structures that progress from an immature state (A) to a mature state (B). (A) The immature state is characterized by a central core where LFA-1 and ICAM-1 accumulate, while peptide/MHC complexes are located in a peripheral region. (B) Within a few minutes this pattern is reversed: TCR and peptide/MHC tend to accumulate in the centre of the synapse while LFA-1/ICAM-1 are excluded. TCR-mediated signal transduction is initially localized at the periphery of the synapse (A), later it moves towards the centre of the synapse (B).

Figure 3. Schematic representation of the mature IS. The IS is composed of three major regions: the cSMAC containing TCR and accessory molecules, the pSMAC containing adhesion molecules and the dSMAC containing large and heavily glycosylated trans-membrane proteins. Intracellular signalling components and cytoskeleton components segregate in parallel with surface molecules within the three major zones of the IS.

Figure 4. En face view of the mature IS. The figure represents a schematic view of the three-dimensional localization of IS components. Data are obtained using three-dimensional reconstruction of high-resolution images obtained either by confocal laser scanning microscopy or by de-convolution of widefield epifluorescence microscopy. Only the localization of major surface molecules is shown.

Figure 5. Schematic representation of the signalling pathways coupled to the engagement of TCR and accessory molecules at the IS. Four main signalling pathways that converge to the T-cell nucleus for the activation of cytokine gene transcription are identified by four different colour codes: the  Ca²⁺/calcineurin pathway in violet, the PKC pathway in orange, the Ras/ERK pathway in green and the Vav-1/Jun pathway in blue. All adaptor proteins are in brown.