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.
Key Words: T cell; kinase; adaptor; phosphatase; immunodeficiency; autoimmunity.
c1 Molecular Immunology Section, Department of Immunology, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK. Tel: +44 (0)20 8383 8421; Fax: +44 (0)20 8383 8434; E-mail: firstname.lastname@example.org