Immune synapse formation promotes lipid peroxidation and MHC-I upregulation in licensed dendritic cells for efficient priming of CD8+ T cells

Antigen cognate dendritic cell (DC)-T cell synaptic interactions drive activation of T cells and instruct DCs. Upon receiving CD4 + T cell help, post-synaptic DCs (psDCs) are licensed to generate CD8 + T cell responses. However, the cellular and molecular mechanisms that enable psDCs licensing remain unclear. Here, we describe that antigen presentation induces an upregulation of MHC-I protein molecules and increased lipid peroxidation on psDCs in vitro and in vivo. We also show that these events mediate DC licensing. In addition, psDC adoptive transfer enhances pathogen-specific CD8 + T responses and protects mice from infection in a CD8 + T cell-dependent manner. Conversely, depletion of psDCs in vivo abrogates antigen-specific CD8 + T cell responses during immunization. Together, our data show that psDCs enable CD8 + T cell responses in vivo during vaccination and reveal crucial molecular events underlying psDC licensing. CD4 + T cells have been shown to be important in CD8 + T cell responses through a process of DC:T cell interaction. Here the authors further characterise this DC:T cell interaction and show that after CD4 + T cell help these post-synaptic DCs have increased lipid peroxidation and increased MHC class I proteins associated with increased cross-presentation function.