Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells
AE Morelli, AT Larregina, WJ Shufesky, MLG Sullivan… - Blood, 2004 - ashpublications.org
AE Morelli, AT Larregina, WJ Shufesky, MLG Sullivan, DB Stolz, GD Papworth…
Blood, 2004•ashpublications.orgExosomes are nanovesicles released by leukocytes and epithelial cells. Although their
function remains enigmatic, exosomes are a source of antigen and transfer functional major
histocompatibility complex (MHC)–I/peptide complexes to dendritic cells (DCs) for CD8+ T-
cell activation. Here we demonstrate that exosomes also are internalized and processed by
immature DCs for presentation to CD4+ T cells. Endocytosed exosomes are sorted into the
endocytic compartment of DCs for processing, followed by loading of exosome-derived …
function remains enigmatic, exosomes are a source of antigen and transfer functional major
histocompatibility complex (MHC)–I/peptide complexes to dendritic cells (DCs) for CD8+ T-
cell activation. Here we demonstrate that exosomes also are internalized and processed by
immature DCs for presentation to CD4+ T cells. Endocytosed exosomes are sorted into the
endocytic compartment of DCs for processing, followed by loading of exosome-derived …
Abstract
Exosomes are nanovesicles released by leukocytes and epithelial cells. Although their function remains enigmatic, exosomes are a source of antigen and transfer functional major histocompatibility complex (MHC)–I/peptide complexes to dendritic cells (DCs) for CD8+ T-cell activation. Here we demonstrate that exosomes also are internalized and processed by immature DCs for presentation to CD4+ T cells. Endocytosed exosomes are sorted into the endocytic compartment of DCs for processing, followed by loading of exosome-derived peptides in MHC-II molecules for presentation to CD4+ T cells. Targeting of exosomes to DCs is mediated via milk fat globule (MFG)–E8/lactadherin, CD11a, CD54, phosphatidylserine, and the tetraspanins CD9 and CD81 on the exosome and αv/β3 integrin, and CD11a and CD54 on the DCs. Circulating exosomes are internalized by DCs and specialized phagocytes of the spleen and by hepatic Kupffer cells. Internalization of blood-borne allogeneic exosomes by splenic DCs does not affect DC maturation and is followed by loading of the exosome-derived allopeptide IEα52-68 in IAb by host CD8α+ DCs for presentation to CD4+ T cells. These data imply that exosomes present in circulation or extracellular fluids constitute an alternative source of self- or allopeptides for DCs during maintenance of peripheral tolerance or initiation of the indirect pathway of allorecognition in transplantation.
ashpublications.org