T-cell signalling and immune system disorders.
T-cell receptor (TCR) engagement initiates intracellular signalling cascades that lead to T-cell proliferation, cytokine production and differentiation into effector cells. These cascades comprise an array of protein-tyrosine kinases, phosphatases, GTP-binding proteins and adaptor proteins that regulate generic and specialised functions. The integration of these signals is essential for the normal development, homeostasis and function of T cells. Defects in a single mediator can produce T cells that are unable to participate fully in an immune response and/or that mount an inappropriate response, which leads to immunodeficiency, autoimmunity or leukaemia/lymphomas. This review highlights some of the key players in T-cell signalling and their involvement in the development of various clinical disease states. Some of these immune-specific signalling proteins are attractive potential targets in the development of therapies to augment T-cell responses to antigen or tumours, and to treat immune cell disorders.
Wilkinson
Beverley
B
Molecular Immunology Section, Department of Immunology, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
Downey
Jocelyn S
JS
Rudd
Christopher E
CE
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007154:Immune System Diseases / Q000276:immunology* / Q000628:therapy; D051379:Mice; D010770:Phosphotransferases / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D010770:Phosphotransferases; D017027:Protein Tyrosine Phosphatases