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.

Automated summary

Antigen presentation induces upregulation of MHC-I protein molecules and increased lipid peroxidation on psDCs, mediating DC licensing. Adoptive transfer of psDC enhances pathogen-specific CD8(+) T cell responses and protects mice from infection. The study reveals crucial molecular events underlying psDC licensing.