Dendritic cell phagosomes recruit GRASP55 for export of antigen-loaded MHC molecules

Dendritic cells (DCs) present exogenous antigens via major histocompatibility complex class I (MHC-I) and MHC class II (MHC-II) molecules, activating CD8+ and CD4+ T cells. A critical but poorly understood step in this process is the trafficking of peptide-loaded MHC molecules from the endocytic sys...

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Detalles Bibliográficos
Autores: Cebrian Lazart, Ignacio, Dinamarca, Sofía, Pena Rodriguez, Maria, Priego, Elena, Brouwers, Nathalie, Barends, Martina, Brunnberg, Jamina, Tampé, Robert, Blanchard, Nicolas, Sancho, David, Malhotra, Vivek
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/70000
Acceso en línea:http://hdl.handle.net/10230/70000
http://dx.doi.org/10.1016/j.celrep.2025.115333
Access Level:acceso abierto
Palabra clave:CP: Immunology
GRASP55
MHC transport
Antigen presentation
Dendritic cells
Phagosomes
Descripción
Sumario:Dendritic cells (DCs) present exogenous antigens via major histocompatibility complex class I (MHC-I) and MHC class II (MHC-II) molecules, activating CD8+ and CD4+ T cells. A critical but poorly understood step in this process is the trafficking of peptide-loaded MHC molecules from the endocytic system to the cell surface. In this study, we demonstrate that the Golgi reassembly-stacking protein of 55 kDa (GRASP55), which has been shown to have no role in stacking, is essential for antigen presentation. Using soluble, bead-coated, and bacterial-bound antigens, we found significantly impaired exogenous antigen presentation in GRASP55-deficient bone-marrow-derived DCs (BMDCs). Notably, GRASP55 was recruited to late phagosomes, and our data suggest that it is crucial for sorting MHC-I and MHC-II molecules, facilitating their trafficking to the plasma membrane. Our findings highlight the vital role of GRASP55 in the intracellular transport of MHC molecules bound to their respective peptides during exogenous antigen presentation.