Inhibition of T-Cell Receptor Signal Transduction and Viral Expression by the Linker for Activation of T Cells-Interacting p12 I Protein of Human T-Cell Leukemia/Lymphoma Virus Type 1
| Autor: | Miroslav Dundr, Christophe Nicot, Valerio W. Valeri, Genoveffa Franchini, Risaku Fukumoto, Anthony Adams, Lawrence E. Samelson |
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| Rok vydání: | 2007 |
| Předmět: |
viruses
CD3 Immunology Receptors Antigen T-Cell Down-Regulation Linker for Activation of T cells Biology Microbiology Cell Line Immunological synapse Membrane Microdomains Virology Humans Cytotoxic T cell Viral Regulatory and Accessory Proteins Phosphorylation Proto-Oncogene Proteins c-vav Adaptor Proteins Signal Transducing Human T-lymphotropic virus 1 NFATC Transcription Factors Phospholipase C gamma ZAP70 T-cell receptor Membrane Proteins Oncogene Proteins Viral Virus-Cell Interactions Cell biology Insect Science biology.protein Clone (B-cell biology) Gene Deletion CD8 Signal Transduction Transcription Factors |
| Zdroj: | Journal of Virology. 81:9088-9099 |
| ISSN: | 1098-5514 0022-538X |
| Popis: | The p12 I protein of human T-cell leukemia/lymphoma virus type 1 (HTLV-1) is a small oncoprotein that increases calcium release following protein kinase C activation by phorbol myristate acetate, and importantly, this effect is linker for activation of T cells (LAT) independent. Here, we demonstrate that p12 I inhibits the phosphorylation of LAT, Vav, and phospholipase C-γ1 and decreases NFAT (nuclear factor of activated T cells) activation upon engagement of the T-cell receptor (TCR) with anti-CD3 antibody. Furthermore, we demonstrate that p12 I localizes to membrane lipid rafts and, upon engagement of the TCR, relocalizes to the interface between T cells and antigen-presenting cells, defined as the immunological synapse. A p12 I knockout molecular clone of HTLV-1 expresses more virus upon antigen stimulation than the isogenic wild type, suggesting that, by decreasing T-cell responsiveness, p12 I curtails viral expression. Thus, p12 I has contrasting effects on TCR signaling: it down-regulates TCR in a LAT-dependent manner on one hand, and on the other, it increases calcium release in a LAT-independent manner. The negative regulation of T-cell activation by p12 I may have evolved to minimize immune recognition of infected CD4 + T cells, to impair the function of infected cytotoxic CD8 + T cells, and to favor viral persistence in the infected host. |
| Databáze: | OpenAIRE |
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