Mechanisms of transmembrane signalling in human T cell activation.
Several monoclonal antibodies directed against a number of T cell surface molecules are used to elucidate the role of these molecules (cell surface molecules) in T cell activation. The activation of T cells via these molecules are both antigen-dependent (CD3/TcR complex) and antigen-independent. Irrespective of their antigen dependency, these monoclonal antibodies activate T cells by a classical signal transduction pathway, in which the binding of monoclonal antibodies to their cell surface receptors leads to activation of phospholipase C resulting in the depolarization of plasma membrane, hydrolysis of IP2 and IP3 and DAG, the 'second messengers'. IP3 leads to mobilization of intracellular calcium to contribute to an increase in [Ca++]i, whereas DAG causes activation and translocation of PKC and an increasing apparent affinity for Ca++. The role of IP4 in the mobilization of intracellular calcium is emerging. In addition, influx of extracellular calcium also contributes to increase in [Ca++]i. The increase in [Ca++]i following activation via some T cell surface antigen is predominantly due to intracellular mobilization of Ca++ (e.g. CD3/TcR complex), whereas activation via other T cell surface antigen, the increase in [Ca++]i is almost entirely due to an influx of extracellular calcium (e.g. CD5 antigen). All these molecules activate autocrine system of T cell growth, namely IL-2 production, IL-2 receptor expression and T cell proliferation.
Gupta
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Division of Basic and Clinical Immunology, University of California, Irvine 92717.
D015703:Antigens, CD / Q000276:immunology*; D002462:Cell Membrane / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D011948:Receptors, Antigen, T-Cell