Dendritic cell phagosomes recruit GRASP55 for efficient transport of MHC molecules to the plasma membrane during exogenous antigen presentation

IGNACIO CEBRIÁN; NATHALIE BROUWERS; NICOLAS BLANCHARD; VIVEK MALHOTRA

Niza

Congreso; Joint Annual Meetings of the French Society for Immunology and the Frenc Cytometry Association; 2022

SFI-AFC

Introduction: 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. There is a good understanding of the general aspects of these antigen presentation pathways, but many important intracellular features, as well as their molecular regulators, remain unknown. Specially, the last steps that control the efficient transport of MHC/peptide complexes from the endocytic system to the plasma membrane remain poorly understood. We present a surprising finding that the Golgi reassembly-stacking protein of 55 kDa (GRASP55) plays an essential role in antigen presentation. Objective: The objective of this work is to evaluate the involvement of GRASP55 in the intracellular transport of MHC/peptide complexes during exogenous antigen presentation by DCs. Results: In this study, 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-deficientDCs, 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. Conclusion: 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.