GRASP55 controls the transport of MHC-loaded molecules during exogenous antigen presentation

CEBRIÁN, IGNACIO

Mendoza

Workshop; Immunology Workshop 2023; 2023

Universidad Nacional de Cuyo

Dendritic cells (DCs) are highly adapted to present exogenous antigen-derived peptides in association with MHC class I and II molecules to trigger the activation of CD8+ and CD4+ T lymphocytes, respectively. The former process is referred to as cross-presentation, while the latter corresponds to the classical MHC-II presentation pathway. For both, the endocytic route plays determinant functions that allow optimal antigen processing and efficient loading of MHC molecules before the final transport of these complexes to the cell surface. In this study, we present a surprising finding that the Golgi reassembly-stacking protein of 55 kDa (GRASP55) plays an essential role in antigen presentation. We used bone marrow-derived DCs (BMDCs) from WT and GRASP55-/- C57BL/6 mice, and our data show that both cross-presentation and MHC-II antigen presentation are significantly inhibited in GRASP55-deficient DCs, as compared to control DCs. We show that GRASP55 is recruited to late DC phagosomes, and this recruitment is crucial for the efficient sorting of loaded MHC-I and II molecules from DC phagosomes to the plasma membrane. Our findings provide compelling evidence that GRASP55 plays a major role in the intracellular transport of MHC-I and II molecules, and its expression in DCs is essential for the competent presentation of exogenous antigens.