Lysosomal and endosomal compartments in antigen-presenting cells

The lysosomal and endosomal compartments in antigen-presenting cells (APCs) constitute a critical subcellular system responsible for the internalization, processing, and presentation of exogenous antigens (Roche & Furuta, 2015, Nature Reviews Immunology). These compartments, which include early endosomes, late endosomes, and lysosomes, provide the acidic environment and proteolytic enzymes (such as cathepsins) necessary to degrade proteins into peptides (Watts, 2012, Annual Review of Immunology). These peptides are then loaded onto MHC class II molecules for presentation to T cells, a process essential for initiating adaptive immune responses. Additionally, these compartments house various pattern recognition receptors, such as Toll-like receptors 7 and 9, which sense nucleic acids (Kuznik et al., 2011, Journal of Immunology). Pharmacological modulation of these compartments, typically through the use of lysosomotropic agents like hydroxychloroquine, aims to increase the internal pH, thereby inhibiting antigen processing and downstream inflammatory signaling in autoimmune conditions like systemic lupus erythematosus and rheumatoid arthritis (Schrezenmeier & Dörner, 2020, Nature Reviews Rheumatology). This system is also a target for pathogens that exploit endocytic pathways for cellular entry.

Other names

Endo-lysosomal systemEndocytic pathwayMHC class II compartmentMIIC

Inhibition of endosomal acidification and lysosomal enzyme activity, leading to impaired antigen processing and presentation, as well as reduced Toll-like receptor (TLR) signaling.