S-Space College of Medicine/School of Medicine (의과대학/대학원) Immunology (면역학전공) Journal Papers (저널논문_면역학전공)
Cross-linking of 4-1BB activates TCR-signaling pathways in CD8+ T lymphocytes
- Nam, K. O.; Kang, H.; Shin, S. M.; Cho, K. H.; Kwon, B.; Kwon, B. S.; Kim, S. J.; Lee, H. W.
- Issue Date
- American Association of Immunologists
- J Immunol. 2005 Feb 15;174(4):1898-905.
- 4-1BB Ligand; Animals; Antibodies, Monoclonal/metabolism; Antigens, CD; Antigens, CD137; CD8-Positive T-Lymphocytes/drug effects/enzymology/*immunology/*metabolism; Calcium/metabolism; Cetomacrogol; Cyclosporine/pharmacology; Detergents; Growth Inhibitors/pharmacology; Intracellular Fluid/metabolism; Ligands; Lymphocyte Activation/drug effects/*immunology; Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism; Membrane Microdomains/enzymology/metabolism; Mice; Mice, Inbred BALB C; Phosphotyrosine/metabolism; Protein Transport/immunology; Pyrimidines/pharmacology; Receptors, Antigen, T-Cell/metabolism/*physiology; Receptors, Nerve Growth Factor/antagonists &; inhibitors/*immunology/*metabolism/physiology; Receptors, Tumor Necrosis Factor/antagonists &; inhibitors/*immunology/*metabolism/physiology; Signal Transduction/drug effects/*immunology; Solubility; TNF Receptor-Associated Factor 2/metabolism; Tumor Necrosis Factor-alpha/metabolism; beta-Cyclodextrins/pharmacology
- Cross-linking of 4-1BB, a member of the TNFR family, increased tyrosine phosphorylation of TCR-signaling molecules such as CD3epsilon, CD3zeta, Lck, the linker for activation of T cells, and SH2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76). In addition, incubation of activated CD8+ T cells with p815 cells expressing 4-1BBL led to redistribution of the lipid raft domains and Lck, protein kinase C-theta;, SLP-76, and phospholipase C-gamma1 (PLC-gamma1) on the T cell membranes to the areas of contact with the p815 cells and recruitment of 4-1BB, TNFR-associated factor 2, and phospho-tyrosine proteins to the raft domains. 4-1BB ligation also caused translocation of TNFR-associated factor 2, protein kinase C-theta;, PLC-gamma1, and SLP-76 to detergent-insoluble compartments in the CD8+ T cells, and cross-linking of 4-1BB increased intracellular Ca2+ levels apparently by activating PLC-gamma1. The redistribution of lipid rafts and Lck, as well as translocation of PLC-gamma1, and degradation of IkappaB-alpha in response to 4-1BB were inhibited by disrupting the formation of lipid rafts with methyl-beta-cyclodextrin. These findings demonstrate that 4-1BB is a T cell costimulatory receptor that activates TCR-signaling pathways in CD8+ T cells.
- 0022-1767 (Print)
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