Browse

Cross-linking of 4-1BB activates TCR-signaling pathways in CD8+ T lymphocytes

Cited 0 time in Web of Science Cited 0 time in Scopus
Authors
Nam, K. O.; Kang, H.; Shin, S. M.; Cho, K. H.; Kwon, B.; Kwon, B. S.; Kim, S. J.; Lee, H. W.
Issue Date
2005-02-09
Publisher
American Association of Immunologists
Citation
J Immunol. 2005 Feb 15;174(4):1898-905.
Keywords
4-1BB LigandAnimalsAntibodies, Monoclonal/metabolismAntigens, CDAntigens, CD137CD8-Positive T-Lymphocytes/drug effects/enzymology/*immunology/*metabolismCalcium/metabolismCetomacrogolCyclosporine/pharmacologyDetergentsGrowth Inhibitors/pharmacologyIntracellular Fluid/metabolismLigandsLymphocyte Activation/drug effects/*immunologyLymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolismMembrane Microdomains/enzymology/metabolismMiceMice, Inbred BALB CPhosphotyrosine/metabolismProtein Transport/immunologyPyrimidines/pharmacologyReceptors, Antigen, T-Cell/metabolism/*physiologyReceptors, Nerve Growth Factor/antagonists &inhibitors/*immunology/*metabolism/physiologyReceptors, Tumor Necrosis Factor/antagonists &inhibitors/*immunology/*metabolism/physiologySignal Transduction/drug effects/*immunologySolubilityTNF Receptor-Associated Factor 2/metabolismTumor Necrosis Factor-alpha/metabolismbeta-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

http://hdl.handle.net/10371/22613
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Immunology (면역학전공)Journal Papers (저널논문_면역학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse