T cell receptor activation

These authors identified novel serine kinases activated by cytokines and chemokines in T cells using PAP-1, and verified MAP kinase dependent IL-16 secretion in T-cell receptor-activated T cells. 

The binding of the antigen to the T-cell receptor activates the T-cell which synthesises and secretes cytokines. 

The rise in Ca2+ caused by ligand binding to T cell receptors activates calcineurin s phosphatase activity, which dephosphorylates cytoplasmic NF-ATc proteins. Depho-sphorylated NF-ATc enters the nucleus and binds to DNA in cooperation with other transcription factors, e. g., AP-1. In this way, many target genes in diverse tissues can be activated. 

Ferran C, Dy M, Sheehan K, Schreiber R, Grau G, Bluestone J, Bach JF, Chatenoud L. Cascade modulation by anti-tumor necrosis factor monoclonal antibody of interferon-y, interleukin 3 and interleukin 6 release after triggering of the CD3/T cell receptor activation pathway. Eur J Immunol 1991 21(10) 2349-2353. 

AMPK can also be activated by a Ca2+-mediated pathway involving phosphorylation at Thr-172 by the Ca2+/calmodulin-dependent protein kinase, CaMKK 3. CaMKKa and CaMKK 3 were discovered as the upstream kinase for the calmodulin-dependent protein kinases-1 and -IV they both activate AMPK in a Ca2+/ calmodulin-dependent manner in cell-free assays, although CaMKK 3 appears to much more active against AMPK in intact cells. Expression of CaMKKa and CaMKK(3 primarily occurs in neural tissues, but CaMKKp is also expressed in some other cell types. Thus, the Ca2+-mediated pathway for AMPK activation has now been shown to occur in response to depolarization in rat neuronal tissue, in response to thrombin (acting via a Gq-coupled receptor) in endothelial cells, and in response to activation of the T cell receptor in T cells. 

Cytokines. Figure 1 Inhibition of cytokine synthesis during activation of the specific immune system. The monoclonal antibodies Muromonab and Basiliximab are specific for the CD3 complex of the T-cell receptor, and for the IL-2 receptor on lymphocytes, respectively. Cyclosporin and Tacrolimus inhibit activation of cytoplasmic NF-AT, a transcription factor essential for activation of the IL-2 gene ( NFAT Family of Transcription Factors). Sirolimus interferes with mTOR signaling and inhibits IL-2 dependent proliferation. Red pharmaka, blue target proteins. 

Bacterial or viral proteins linking T-cell receptors and MHC molecules through simultaneous interaction with the constant domains of all MHC class II molecules and of T-cell receptor (3-chains. Hence, superantigens are polyclonal T-cell activators most likely involved in the development of autoimmune diseases. 

CD lb Known to be present on thymocytes and dendritic cells CDlc Isoform c also known as non-classical MHC class I-like surface antigen present on thymocytes CD2 Defines T cells involved in antigen non-specific cell activation CD3 Also known as T cell receptor-associated surface glycoprotein on T cells CD4 Defines MHC class Il-restricted T cell subsets... 

An APC is a cell that displays a foreign antigen complex with MHC on its cell surface. Its major responsibility is to present these foreign antigens to T cells. T cells can identify this complex using their T-cell receptors (TCRs). There are three main types of APCs dendritic cells, macrophages, and activated B cells. Dendritic cells (DCs) are present in tissues that... 

The development of effector T cells following activation by antigen-presenting cells also requires the interaction of another receptor-ligand pair. CD40 molecules on antigen-presenting cells are required to bind... 

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