Similarities between the T cell–T cell VS and IS. The upper images of A and B show stylized features of synapses formed between T cells in the VS (A) and the IS (B). The VS schematic (A) is based on a composite of known features of the HIV-1 and HTLV-1 T cell VSs and highlights features in common with, and divergent from, the IS. Within the VS, Env ligates CD4 and CXCR4 in the target cell and ICAM-1 engages LFA-1 in the target cell. Gag associated with the viral genome present within the effector cell is recruited along microtubules to the site of cell-cell contact and moves across the central zone of the synapse into the target cell. In the target cell, LFA-1–talin complexes and CD4 and CXCR4 are recruited in an actin-dependent manner to the VS. In the IS (B), LFA-1–talin complexes form the pSMAC, whereas the T cell receptor (TCR) is recruited to the cSMAC, into which cytotoxic granules are secreted in a microtubule-dependent manner. In the target cell, ICAM-1 engages LFA-1 and peptide–MHC-I complexes ligate the TCR of the effector cell. The lower parts of both panels illustrate a simplified schematic of the molecular arrangements present in the VS (A) and IS (B). The VS is shown in its partially disordered form with Env-receptor complexes interspersed with ligated adhesion molecules.