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

免疫突触的形成促进已激活树突状细胞中的脂质过氧化和MHC-I上调,从而有效启动CD8+ T细胞。

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作者:Diego Calzada-Fraile ,Salvador Iborra ,Marta Ramírez-Huesca ,Inmaculada Jorge ,Enrico Dotta ,Elena Hernández-García ,Noa Martín-Cófreces ,Estanislao Nistal-Villán ,Esteban Veiga ,Jesús Vázquez ,Giulia Pasqual ,Francisco Sánchez-Madrid

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.

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