The Salmonella effector SteD Mediates MARCH8-dependent ubiquitination of MHC II molecules and inhibits T cell activation
| Autor: | Bayer-Santos, Ethel, Durkin, Charlotte H., Rigano, Luciano A., Kupz, Andreas, Alix, Eric, Cerny, Ondrej, Jennings, Elliott, Liu, Mei, Ryan, Aindrias S., Lapaque, Nicolas, Kaufmann, Stefan H. E., Holden, David W. |
|---|---|
| Přispěvatelé: | MRC Centre for Molecular Bacteriology and Infection, Queen Mary University of London (QMUL), Centre for Biosecurity and Tropical Infectious Diseases, Australian Institute of Tropical Health and Medicine, James Cook University, Department of Immunology, University of Toronto, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Medical Research Council [MR/K027077/1], Wellcome Trust [095484/Z/11/Z], CAPES Fellowship [9236/13-9] |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | Cell Host and Microbe Cell Host and Microbe, Elsevier, 2016, 20 (5), pp.584-595. ⟨10.1016/j.chom.2016.10.007⟩ Cell Host & Microbe |
| ISSN: | 1931-3128 |
| DOI: | 10.1016/j.chom.2016.10.007⟩ |
| Popis: | SummaryThe SPI-2 type III secretion system (T3SS) of intracellular Salmonella enterica translocates effector proteins into mammalian cells. Infection of antigen-presenting cells results in SPI-2 T3SS-dependent ubiquitination and reduction of surface-localized mature MHC class II (mMHCII). We identify the effector SteD as required and sufficient for this process. In Mel Juso cells, SteD localized to the Golgi network and vesicles containing the E3 ubiquitin ligase MARCH8 and mMHCII. SteD caused MARCH8-dependent ubiquitination and depletion of surface mMHCII. One of two transmembrane domains and the C-terminal cytoplasmic region of SteD mediated binding to MARCH8 and mMHCII, respectively. Infection of dendritic cells resulted in SteD-dependent depletion of surface MHCII, the co-stimulatory molecule B7.2, and suppression of T cell activation. SteD also accounted for suppression of T cell activation during Salmonella infection of mice. We propose that SteD is an adaptor, forcing inappropriate ubiquitination of mMHCII by MARCH8 and thereby suppressing T cell activation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|