The Actin Cytoskeleton and Lymphocyte Activation

" organized contacts " at the interfaces of physical contact between T cells and APCs (Monks et al., 1997). areas between T cells and APCs incubated with anti-genic peptides indicate that a SMAC is organized into Stanford, California 941010-0269 distinct spatial domains (Monks et al., 1998). The central area of a SMAC contains the TCR, CD3, p56 lck and p59 fyn kinases, and protein kinase C (PKC)h, while the periph-All stages in lymphocyte life and activation are associated with profound changes in cell morphology that eral regions are enriched in the adhesion molecule LFA1 depend on a functional tubulin and actomyosin cytoskel-and the cytoskeletal protein talin (Figure 1B). Based on eton. Lymphocytes migrate through blood and lymph measurements of physical dimensions and molecular vessels, transgress vessel walls and extracellular matrix interactions, it has also been proposed that the corecep-spaces, home into lymphoid organs, interact with anti-tors CD4 and CD8, the costimulatory molecule CD28, gen-presenting cells (APCs), and adhere to target cells. and the adhesion molecule CD2 may cosegregate with During lymphocyte maturation, developing T and B cell the central SMAC domain, whereas the phosphatase precursors are in continuous contact with stromal cells CD45 and adhesion molecule CD43 might be excluded of the thymic or bone marrow microenvironments, and from the central contact zone (Shaw and Dustin, 1997). these physical contacts are crucial prerequisites for dif-The segregation of molecules in SMACs is mirrored in ferentiation and selection. Since many signaling mole-the orientation of molecules on the APC surface. MHC cules are associated with cytoskeletal scaffolds, the class II molecules and the LFA1-ligand ICAM1 congre-cytoskeletal structure and scaffold geometries can di-gate in the corresponding contact zone of the APC rectly regulate the molecular dynamics of signaling and (Monks et al., 1998; Wü lfing et al., 1998). When T cells biochemical responses. This minireview examines the were activated with altered peptides that did not trigger emerging role of the actin cytoskeleton as an integral cytokine production or T cell proliferation, CD3 and talin component of lymphocyte activation. formed molecular clusters but did not segregate into