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http://purl.uniprot.org/citations/24337741http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24337741http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/24337741http://www.w3.org/2000/01/rdf-schema#comment"CD8(+) CTLs are adept at killing virally infected cells and cancer cells and releasing cytokines (e.g., IFN-γ) to aid this response. However, during cancer and chronic viral infections, such as with HIV, this CTL response is progressively impaired due to a process called T cell exhaustion. Previous work has shown that the glycoprotein T cell Ig and mucin domain-containing protein 3 (Tim-3) plays a functional role in establishing T cell exhaustion. Tim-3 is highly upregulated on virus and tumor Ag-specific CD8(+) T cells, and antagonizing Tim-3 helps restore function of CD8(+) T cells. However, very little is known of how Tim-3 signals in CTLs. In this study, we assessed the role of Tim-3 at the immunological synapse as well as its interaction with proximal TCR signaling molecules in primary human CD8(+) T cells. Tim-3 was found within CD8(+) T cell lipid rafts at the immunological synapse. Blocking Tim-3 resulted in a significantly greater number of stable synapses being formed between Tim-3(hi)CD8(+) T cells and target cells, suggesting that Tim-3 plays a functional role in synapse formation. Further, we confirmed that Tim-3 interacts with Lck, but not the phospho-active form of Lck. Finally, Tim-3 colocalizes with receptor phosphatases CD45 and CD148, an interaction that is enhanced in the presence of the Tim-3 ligand, galectin-9. Thus, Tim-3 interacts with multiple signaling molecules at the immunological synapse, and characterizing these interactions could aid in the development of therapeutics to restore Tim-3-mediated immune dysfunction."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.org/dc/terms/identifier"doi:10.4049/jimmunol.1302663"xsd:string
http://purl.uniprot.org/citations/24337741http://purl.org/dc/terms/identifier"doi:10.4049/jimmunol.1302663"xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/author"Mujib S."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/author"Mujib S."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/author"Clayton K.L."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/author"Clayton K.L."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/author"Ostrowski M.A."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/author"Ostrowski M.A."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/author"Chew G.M."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/author"Chew G.M."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/author"Douglas-Vail M.B."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/author"Douglas-Vail M.B."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/author"Haaland M.S."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/author"Haaland M.S."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/author"Ndhlovu L.C."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/author"Ndhlovu L.C."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/name"J. Immunol."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/name"J. Immunol."xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/pages"782-791"xsd:string
http://purl.uniprot.org/citations/24337741http://purl.uniprot.org/core/pages"782-791"xsd:string