T-Cell zeta chain expression, phosphorylation and degradation and their role in T-cell signal transduction and immune response regulation in health and disease

Abstract

T-cell zeta chain expression, phosphorylation and degradation and their role in T-cell signal transduction and immune response regulation in health and disease. Zeta chain is a stable constituent of the antigen specific T-cell receptor and its phosphorylation is one of the earliest and key events in the T-cell signal transduction. Zeta chain phosphorylation is strictly controlled by the action of sarcoma-family kinases and also by phosphatases, indicating its crucial role in antigen specific T-cell activation. Furthermore, after its phosphorylation and T-cell activation, xi-chain is ubiquitylated and degraded, a fact suggesting that its level on T-cell surface is also under control and contribute to the regulation of an initiated immune response. Zeta chain expression and/or phosphorylation seems to be of great importance in many clinical conditions from the pathogenesis of various types of cancer to the immunosuppressive state in dialysis patients. Its levels are also affected by chronic inflammation. In addition to its role in the antigen specific signal transduction, xi-chain is present only in T-cells and natural killer cells, making it a possible target for immunotherapeutic applications. The recent discovery of specific inhibitors of xi-chain phosphorylation opens new horizons for future research and for possible therapeutic interventions in various clinical conditions.