CD97 stabilises the immunological synapse between dendritic cells and T cells and is targeted for degradation by the Salmonella effector SteD

Author summary Salmonella enterica is the causative agent of very large numbers of serious and life-threatening diseases in humans and livestock throughout the world. Clearance of S. enterica from the host is dependent on T cell-mediated immune responses. We show here that the Salmonella SPI-2 type III secretion system effector SteD inhibits activation of T cells by reducing contacts between infected antigen-presenting cells and T cells. This is mediated by degradation of an adhesion G protein-coupled receptor CD97. Our work reveals that CD97 stabilizes the interaction between antigen-presenting cells and T cells and identifies this process as a direct target for bacterial pathogens. The Salmonella enterica effector SteD depletes mature MHC class II (mMHCII) molecules from the surface of infected antigen-presenting cells through ubiquitination of the cytoplasmic tail of the mMHCII beta chain. This requires the Nedd4 family HECT E3 ubiquitin ligase Wwp2 and a tumor-suppressing transmembrane protein adaptor Tmem127. Here, through a proteomic screen of dendritic cells, we found that SteD targets the plasma membrane protein CD97 for degradation by a similar mechanism. SteD enhanced ubiquitination of CD97 on K555 and mutation of this residue eliminated the effect of SteD on CD97 surface levels. We showed that CD97 localises to and stabilises the immunological synapse between dendritic cells and T cells. Removal of CD97 by SteD inhibited dendritic cell-T cell interactions and reduced T cell activation, independently of its effect on MHCII. Therefore, SteD suppresses T cell immunity by two distinct processes.

Automated summary

The bacterium Salmonella enterica inhibits T cell immune response by affecting T cell activation, mainly through degradation of the CD97 protein to reduce contacts between antigen-presenting cells and T cells. Additionally, Salmonella effector SteD depletes mature MHCII molecules by enhancing ubiquitination of CD97, which affects dendritic cell-T cell interactions independent of its effect on MHCII.