<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Regulation of human lymphocytes by SLAM-related receptors"^^ . "The six members of the SLAM-related receptor family are expressed on many cell types of the immune system and play a role in fine-tuning of immune responses. In this study we investigated the SLAM-related receptors 2B4, NTB-A and CRACC. 2B4 and NTB-A are activating receptors on human natural killer (NK) cells. 2B4 binds to CD48, NTB A is homophilic. The molecular basis for the homophilic NTB A interaction has been identified by crystal structure analysis, but the results have not been tested in functional assays. Using mutational analysis we could show that the residues H54 and S90 are very important for functional homophilic interaction between two NTB A molecules, whereas the residues E37 and Q88 are not. After binding to their ligands 2B4 and NTB A recruit the two adapter molecules SAP and EAT 2. Although many elements of 2B4 and NTB A signaling have been described, the early events in their signal transduction are not fully understood. In this study we could show that in human natural killer cells the phosphorylation of 2B4 and NTB A takes place independently of SAP. However, both receptors need the presence of SAP to trigger cytotoxic responses. The adapter EAT 2 does not bind to the phosphorylated receptors in the absence of SAP. This leads to the conclusion that SAP association with the receptors is the crucial prerequisite for further signaling events, including the recruitment of EAT 2. CRACC is an activating receptor on NK cells triggering cytotoxicity and enhancing cytokine production. The receptor is also expressed on a subset of CD8-positive and few CD4-positive T cells, but the function of CRACC on these cells is unknown. In this study we describe CRACC as co-stimulatory receptor on T cells. Simultaneous engagement of the T cell receptor and CRACC induces expression of activation markers, proliferation and cytokine production. T cell-mediated cytotoxicity is not enhanced by engagement of CRACC. We found that CRACC is expressed mainly on CD8-positive memory T cells, and its expression is induced on CD8-positive T cells by activation. Therefore we suggest that CRACC co-stimulation supports the expansion of activated cells and facilitates the re-activation of memory T cells. Furthermore we could detect CRACC expression on CD4-positive, CD28-negative T cells in patients with unstable angina pectoris. This population appears in patients with chronic inflammatory diseases and amplifies the inflammatory process. We suggest that CRACC co-stimulation could be involved in the continuous activation of these cells, and therefore is a possible therapeutical target."^^ . "2010" . . . . . . . . "Stephan"^^ . "Meinke"^^ . "Stephan Meinke"^^ . . . . . . "Regulation of human lymphocytes by SLAM-related receptors (PDF)"^^ . . . "Dissertation_Stephan_Meinke.pdf"^^ . . . "Regulation of human lymphocytes by SLAM-related receptors (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Regulation of human lymphocytes by SLAM-related receptors (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Regulation of human lymphocytes by SLAM-related receptors (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Regulation of human lymphocytes by SLAM-related receptors (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Regulation of human lymphocytes by SLAM-related receptors (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #10640 \n\nRegulation of human lymphocytes by SLAM-related receptors\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .