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<sup>+</sup> and CD4<sup>+</sup> 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.
Authors
- Sofía Dinamarca
- Robert Tampé (ORCID: https://orcid.org/0000-0002-0403-2160)
- Jamina Brunnberg
- Ignacio Cebrián (ORCID: https://orcid.org/0000-0001-6505-0875)
- Nathalie Brouwers (ORCID: https://orcid.org/0000-0002-9808-9394)
- David Sancho (ORCID: https://orcid.org/0000-0003-2890-3984)
- Moses Rodriguez (ORCID: https://orcid.org/0000-0001-6328-6497)
- Martina Barends
- Vivek Malhotra (ORCID: https://orcid.org/0000-0001-6198-7943)
- Elena Priego (ORCID: https://orcid.org/0000-0002-7560-0620)
- Nicolas Blanchard (ORCID: https://orcid.org/0000-0002-4924-2161)
Institutions
- Goethe University Frankfurt (DE)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- Spanish National Centre for Cardiovascular Research (ES)
- Toulouse Mathematics Institute (FR)
- Barcelona Institute of Science and Technology (ES)
- Centre for Genomic Regulation (ES)
- Instituto de Histología y Embriología de Mendoza (AR)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-02-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.115333
- Citations
- 4
- Primary Topic
- Immunotherapy and Immune Responses
- Type
- article
- Field-Weighted Citation Impact
- 3.19
Funders
- Centres de Recerca de Catalunya
- Alliance Française contre les Maladies Parasitaires
- European Commission
- Agence Nationale de la Recherche
- Generalitat de Catalunya
- Consejo Nacional de Investigaciones Científicas y Técnicas
- Ministerio de Economía y Competitividad
- Ministerio de Ciencia e Innovación
- Agencia Estatal de Investigación
- Spanish National Plan for Scientific and Technical Research and Innovation
- H2020 European Research Council