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

• Published in: Nature communications Vol. 14; no. 1; p. 6772
• Main Authors: Calzada-Fraile, Diego, Iborra, Salvador, Ramírez-Huesca, Marta, Jorge, Inmaculada, Dotta, Enrico, Hernández-García, Elena, Martín-Cófreces, Noa, Nistal-Villán, Estanislao, Veiga, Esteban, Vázquez, Jesús, Pasqual, Giulia, Sánchez-Madrid, Francisco
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.10.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 14/19; 49/79; 631/250/1619/554/1834/1269; 631/250/1619/554/1898/1272; 631/250/21/1566; 631/250/2152/1566; 631/250/2504/133/2505; 64/60; 82/80; Adoptive transfer; Animals; Antigen Presentation; Antigens; CD4 antigen; CD4-Positive T-Lymphocytes; CD8 antigen; CD8-Positive T-Lymphocytes; Cell activation; Dendritic Cells; Histocompatibility Antigens Class I - metabolism; Humanities and Social Sciences; Immunization; Licenses; Licensing; Lipid Peroxidation; Lipids; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Mice; Mice, Inbred C57BL; Molecular modelling; multidisciplinary; Peroxidation; Priming; Proteins; Science; Science (multidisciplinary); Synapses - metabolism; Up-Regulation; Vaccination; Vaccines
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-42480-3

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.