Signaling lymphocytic activation

Chu CY, Chang CP, Chou YT, Handoko HYL, Lo LC, Lin JJ (2013) Development and evaluation of novel phosphotyrosine mimetic inhibitors targeting the Src homology 2 domain of signaling lymphocytic activation molecule (SLAM) associated protein. J Med Chem 56 2841-2849... 

Deehan, M.R., Frame, M.J., Parkhouse, R.M., Seatter, S.D., Reid, S.D., Harnett, M.M. and Harnett, W. (1998) A phosphorylcholine-containing filarial nematode-secreted product disrupts B lymphocyte activation by targeting key proliferative signaling pathways. Journal of Immunology 160, 2692-2699. 

The cells of the immune system communicate with each other particularly intensively. The T-cell receptor plays a central role in the activation of T lymphocytes (see p. 296). The cell at the top has been infected with a virus, and it indicates this by presenting a viral peptide (violet) with the help of a class 1 MHC protein (yellow and green). The combination of the two molecules is recognized by the dimeric T-cell receptor (blue) and converted into a signal that activates the T cell (bottom) and thereby enhances the immune response to the virus. 

LPS can be directly mitogenic for T cells [130], but the antitumoral activity of lymphocytes depends on antigen recognition by their TCR in the context of the major histocompatibility complex (MHC) class I or n. Though LPS enhance it, T lymphocyte activity requires APC [131]. The effect of LPS on T lymphocytes has been shown to depend on monocytes independent of MHC, but to be due to the secretion of costimulatory signals and IL-12 in humans [132]. In vivo, LPS induces principally the proliferation of CD8+ T lymphocytes, but also that of CD4+ T and B lymphocytes through the activation of APC and secretion of IFN 0(7(3 in C57BL/6 mice [133],... 

Incorporation of cytokine in a naive Th lymphocyte receptor activates the route of Janus kinases (JAK1, JAK2, JAK3), transmission proteins for intracellular signals, and activating transcriptions—Signal Transducer and Activator Transcription (STAT)—consequently phosphorylation of receptor tyrosine results. 

Feske, S. 2007. Calcium signaling in lymphocyte activation and disease. Nat. Rev. Immunol. 7, 690-702. Finkel, A. et al. 2006. Population patch-clamp improves data consistency and success rates in the measurement of ionic currents. J. Biomol. Screen. 11,488 496. 

The essential features of lymphocyte activation resemble receptor-mediated signalling by cytokines. In both cases, the receptors lack kinase activities, and signalling firom the receptor on the cell surface to transmitters, and eventually to the nucleus and the genes, is mediated and controlled by cytosolic protein kinases and phosphatases. Recognition... 

Feske S. Calcium signalling in lymphocyte activation and disease. Nat. Rev. Immunol. 2007 7 690-702. 

O Rourke, A.M. and Mescher, M.F. (1992). Cytotoxic T-lymphocyte activation involves a cascade of signalling and adhesion events. Nature 358, 253-255. 

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