Signal transduction and co-stimulatory pathways

Using specific cell surface receptors lymphocytes continuously sample their environment. Maturation of the immune system and initiation of a specific immune response rely on an array of extracellular cues that elicit complex intracellular biochemical signals. Essential molecules involved in signal transduction from immunoreceptors have emerged. After immunoreceptor engagement a core signaling complex is assembled comprising cytoplasmic immunoreceptor chains, kinases of the Src and ZAP70 families and various cytoplasmic and transmembrane adaptor molecules. Further effectors nucleate onto this complex evoking the characteristic responses of lymphocyte activation. Successful maturation of T cells into effector cells relies on the presence of a persistent stimulus presented in an appropriate extracellular environment. Encounter of MHC presented antigenic peptides and their cognate T cell receptors (TCRs) results in the formation of a nanometer intercellular gap between T cells and antigen presenting cells, which is now commonly referred to as the immunological synapse. The synapse is believed to sustain persistent TCR engagement. Its formation requires massive changes in T cell cytoskeletal architecture which essentially relies on signals provided by costimulatory molecules. The well orchestrated interplay between TCR and costimulatory signals decides about successful immune response and tolerance induction or immune failure and autoimmunity.