Endocytic Recycling of MHC Class I Molecules in Non-professional Antigen Presenting and Dendritic Cells

Abstract

Major histocompatibility complex class I (MHC I) molecules are glycoproteins that display peptide epitopes at the cell surface of nucleated cells for recognition by CD8+ T cells. Like other cell surface receptors, MHC class I molecules are continuously removed from the surface followed by intracellular degradation or recycling to the cell surface, in a process likely involving active quality control the mechanism of which remains unknown. The molecular players and pathways involved in internalization and recycling have previously been studied in model cell lines such as HeLa. However, dendritic cells (DCs), which rely on a specialized endocytic machinery that confers them the unique ability to “cross”-present antigens acquired by internalization, may use distinct MHC I recycling pathways and quality control mechanisms. By providing MHC I molecules cross-presenting antigens, these pathways may play an important role in one of the key functions of DCs, priming of T cell responses against pathogens and tumors. In this review, we will focus on endocytic recycling of MHC I molecules in various experimental conditions and cell types. We discuss the organization of the recycling pathway in model cell lines compared to DCs, highlighting the differences in the recycling rates and pathways of MHC I molecules between various cell types, and their putative functional consequences. Reviewing the literature, we find that conclusive evidence for significant recycling of MHC I molecules in primary DCs has yet to be demonstrated. We conclude that endocytic trafficking of MHC class I in DCs remains poorly understood and should be further studied because of its likely role in antigen cross-presentation.

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

“…Most importantly, it favors the formation of coat-independent and dynamin-independent tubulovesicular structures of 60 to 200 nm in diameter [ 78 , 79 ]. Of particular importance is the role of this pathway in modulating the migratory phenotype of many cells [ 80 ] and favoring the continuous replacement of molecules involved in the regulation of extracellular matrix interactions [ 81 , 82 ], immune responses [ 83 , 84 ], and complement system regulation [ 85 , 86 ].…”

Covering All the Bases: Complementary MR1 Antigen Presentation Pathways Sample Diverse Antigens and Intracellular Compartments

“…More recently, membrane contact sites (MCS), defined as points of close physical proximity between organelles which allow the exchange of lipids and ions without membrane fusion, have emerged as a potential explanation for the detection of ER material in phagosomal preparations ( 55 ). Alternative explanations for the presence of a subset of ER proteins in phagosomes include ER-to-phagosome vesicular trafficking and delivery of MHC-I from recycling endosomes ( 45 , 55 , 56 ). Both have been extensively studied in the context of MHC class I-mediated cross-presentation and although many details remain to be elucidated, multiple studies have implicated the ER SNARE Sec22b and its interaction partner Stx4 in the delivery of ER proteins directly to endosomal compartments ( 45 , 57 , 58 ).…”

Destabilizing single chain major histocompatibility complex class I protein for repurposed enterokinase proteolysis

“…The enchained β2m is needed to further destabilize the α chain, as most of the empty α chain remains undigested for unchained pMHC-I protein even at 37 °C. The broad pH range of enterokinase activity between 6.0 and 8.5 also favors screening at pH 6.2 close to the luminal pH and peptide exchange above room temperature 17,18 . Moreover in this work, obvious protein fragments due to non-rescued single chain MHC-I protein with enterokinase is seen at 37 °C.…”

“…Moreover in this work, obvious protein fragments due to non-rescued single chain MHC-I protein with enterokinase is seen at 37 °C. Taken together, the EZ MHC-I assay for the highly polymorphic single chain pMHC-I proteins may be performed under mildly acidic luminal conditions similar to the endosomal compartments 17 .…”