The Salmonella Effector SteD Mediates MARCH8-Dependent Ubiquitination of MHC II Molecules and Inhibits T Cell Activation

Publication date: 9 November 2016
Source:Cell Host & Microbe, Volume 20, Issue 5
Author(s): Ethel Bayer-Santos, Charlotte H. Durkin, Luciano A. Rigano, Andreas Kupz, Eric Alix, Ondrej Cerny, Elliott Jennings, Mei Liu, Aindrias S. Ryan, Nicolas Lapaque, Stefan H.E. Kaufmann, David W. Holden
The 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.

Graphical abstract

Teaser

Dendritic cell infection by Salmonella depletes mature MHC class II (mMHCII) from the cell surface. Bayer-Santos et al. reveal that the Salmonella effector SteD binds the E3 ligase MARCH8 and mMHCII to promote mMHCII ubiquitination and surface depletion. SteD suppressed dendritic cell-mediated T cell activation in vitro and in mice.


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