Fig. 9.36 Interactions of T cells with their targets initially involve nonspecific adhesion molecules. The major initial interaction is between LFa-1 on the T cell, illustrated here as a cytotoxic Cd8 T cell, and ICaM-1 or ICaM-2 on the target cell (top panel). This binding allows the T cell to remain in contact with the target cell and to scan its surface for the presence of specific peptide:MhC complexes. If the target cell does not carry the specific antigen, the T cell disengages (second panel) and can scan other potential targets until it finds the specific antigen (third panel). signaling through the T-cell receptor increases the strength of the adhesive interactions, prolonging the contact between the two cells and stimulating the T cell to deliver its effector molecules. The T cell then disengages (bottom panel).
Chapter 9: T-Cell-Mediated Immunity
Outer ring (red) pSMAC LFA-1:ICAM-1 talin TCR, CD4, CD28 peptide:MHC CD8, PKC-˜Inner circle (green) cSMAC Organization of the immunological synapse T cell dendritic cell pSMAC cSMAC
Fig. 9.37 The area of contact between an effector T cell and another cell forms an immunological synapse. a confocal fluorescence micrograph of the area of contact between a Cd4 T cell and an antigen-presenting cell (apC) (as viewed through one of the cells) is shown. proteins in the contact area between the T cell and the apC form a structure called the immunological synapse, also known as the supramolecular activation complex (sMaC), which is organized into two distinct regions: the outer, or peripheral sMaC (psMaC), indicated by the red ring; and the inner, or central sMaC (csMaC), indicated in bright green. The csMaC is enriched in the T-cell receptor (TCr), Cd4, Cd8, Cd28, Cd2, and pKC-ε. The psMaC is enriched for the integrin LFa-1 and the cytoskeletal protein talin. photograph courtesy of a. Kupfer.
tight binding of LFA-1 to ICAM-1 induced by ligation of the T-cell receptor creates a molecular seal that surrounds the T-cell receptor and its co-receptor (Fig. 9.37). In some cases, the contact surface organizes into two zones: a central zone known as the central supramolecular activation complex (cSMAC) and an outer zone known as the peripheral supramolecular activation complex (pSMAC). The cSMAC contains most of the signaling proteins known to be important in T-cell activation. The pSMAC is notable mainly for the presence of the LFA-1 and the cytoskeletal protein talin, which connects LFA-1 to the actin cytoskeleton (see Section 3-18). The immunological synapse is not a static structure as implied by Fig. 9.37, but is quite dynamic. T-cell receptors move from the periphery into the cSMAC, where they undergo endocytosis through ubiquitin-mediated degradation involving the E3 ligase Cbl (see Section 7-5). Because T-cell receptors are being degraded in the cSMAC, signaling is actually weaker there than in the peripheral contact areas, where microclusters of T-cell receptors are being formed and are highly active (see Section 7-8).