Calzada-Fraile et al. showed that the formation of antigen-induced DC/CD4+ T cell synapses “licensed” post-synaptic DCs (psDC) by upregulation of MHC-I proteins, the ER phagosome pathway of cross-presentation, and ER-associated protein degradation molecules, and increased lipid accumulation and peroxidation, which allowed endosomal antigen escape. psDC cross-presentation enhanced effector and naive CD8+ T cell activation. Adoptive transfer of psDCs protected mice from pathogenic infection by promoting specific effector and memory CD8+ T cell responses. psDC depletion during antigen/alum immunization of mice disabled antigen-specific CD8+ T cell response generation.
Contributed by Paula Hochman
ABSTRACT: 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.