Cebrian, IgnacioDinamarca, SofíaPena Rodríguez, María JesúsPriego, ElenaBrouwers, NathalieBarends, MartinaBrunnberg, JaminaTampé, RobertBlanchard, NicolasSancho, DavidMalhotra, Vivek2025-07-102025-07-102025-02-25Cell Rep. 2025 Feb 25;44(2):115333.https://hdl.handle.net/20.500.12105/26818Dendritic 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.We thank all members of the Malhotra and Blanchard laboratories, especially Emilie Bassot for technical assistance. We thank the joint CRG/UPF FACS Unit at Parc de Recerca Biome` dica de Barcelona (PRBB), the Advanced Light Microscopy Unit at the CRG, and the Cell Imaging facility of the Infinity Institute, especially Sophie Allart, for valuable help. We acknowledge support from the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa, and the CERCA Programme/Generalitat de Catalunya. V.M. is an Institucio´ Catalana de Recerca i Estudis Avanc¸ ats professor at the CRG. Work in the V.M. laboratory is funded by grants from the Spanish Ministry of Economy and Competitiveness (Plan Nacional to V.M., PID2019-105518GB-I00) and the European Research Council Synergy Grant (ERC-2020-SyG - Proposal 951146). I.C. was funded by the Consejo Nacional de Investigaciones Cientı´ficas y Te´ cnicas (CONICET), Argentina, and by project PCI2021-122039-2B, funded by MCIN/AEI/10.13039/501100011033 and the European Union NextGenerationEU/PRTR. N. Blanchard was supported by grants from the PIA PARAFRAP Consortium (ANR-11-LABX0024) and Agence Nationale de la Recherche (ANR-19-CE15-0008 TRANSMIT and ANR-22-CE14-0053 NINTENDO). D.S. was funded by MCIN PID2022-137712OB-I00 MCIN/AEI/10.13039/501100011033 Agencia Estatal de Investigacio´ n, European Union NextGenerationEU/PRTR. This work reflects only the authors’ views, and the EU Community is not liable for any use that may be made of the information contained therein.engVoRCP: ImmunologyGRASP55MHC transportantigen presentationdendritic cellsphagosomes39955774CELL REPORTSopen access