T cell activation and the cytoskeleton

Ligation of the T cell antigen receptor (TCR) stimulates protein tyrosine k inases (PTKs), which regulate intracellular calcium and control the activit y of protein kinase C (PKC) isozymes. PTKs activated by antigen receptors a nd costimulatory molecules also couple to phosphatidylinositol-3 kinase (PI 3K) and control the activity of Ras- and Rho-family GTPases. T cell signal transduction is triggered physiologically by antigen in the context of anti gen presenting cells (APC). The formation of stable and prolonged contacts between T cells and APCs is not neccessary to initiate T cell signaling but is required for effective T cell proliferation and differentiation. The st abilization of the T cell/ APC conjugate is regulated by intracellular sign als induced by antigen receptors and costimulators. These coordinate the re gulation of the actin and microtubule cytoskeleton and organize a specializ ed signaling zone that allows sustained TCR signaling.