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Cross-linking of 4-1BB activates TCR-signaling pathways in CD8+ T lymphocytes
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- Authors
- Issue Date
- 2005-02-09
- Publisher
- American Association of Immunologists
- Citation
- J Immunol. 2005 Feb 15;174(4):1898-905.
- Keywords
- 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
- Abstract
- 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.
- ISSN
- 0022-1767 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15699116
https://hdl.handle.net/10371/22613
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