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

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 and Francisco Sánchez-Madrid ()
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Diego Calzada-Fraile: Centro Nacional de Investigaciones Cardiovasculares
Salvador Iborra: Universidad Complutense de Madrid
Marta Ramírez-Huesca: Centro Nacional de Investigaciones Cardiovasculares
Inmaculada Jorge: Centro Nacional de Investigaciones Cardiovasculares
Enrico Dotta: University of Padova
Elena Hernández-García: Universidad Complutense de Madrid
Noa Martín-Cófreces: Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV)
Estanislao Nistal-Villán: Boadilla del Monte
Esteban Veiga: Centro Nacional de Biotecnología (CNB-CSIC)
Jesús Vázquez: Centro Nacional de Investigaciones Cardiovasculares
Giulia Pasqual: University of Padova
Francisco Sánchez-Madrid: Centro Nacional de Investigaciones Cardiovasculares

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-42480-3

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