Lysosomal and endosomal compartments of antigen-presenting cells

The lysosomal and endosomal compartments of antigen-presenting cells (APCs) are specialized acidic organelles, including early endosomes, late endosomes, and lysosomes, that play a central role in the processing and presentation of exogenous antigens (Roche & Furuta, 2015). These compartments facilitate the degradation of internalized proteins into peptides through the action of acid-dependent proteases, such as cathepsins, which are optimally active at low pH (Schrezenmeier & Dörner, 2020). In the MHC class II compartment (MIIC), these peptides are loaded onto MHC class II molecules for subsequent display on the cell surface to CD4+ T cells, a process essential for initiating adaptive immune responses (Roche & Furuta, 2015). Furthermore, these compartments house endosomal Toll-like receptors (TLRs 7, 8, and 9) that recognize nucleic acids, serving as critical sensors for viral and bacterial pathogens as well as self-nucleic acids in autoimmune contexts (Kuznik et al., 2011). Pharmacological agents like hydroxychloroquine and chloroquine are weak bases that accumulate within these acidic vesicles, increasing the internal pH and thereby inhibiting protease activity and TLR signaling (Schrezenmeier & Dörner, 2020). This interference reduces the presentation of self-antigens and the production of pro-inflammatory cytokines, making these compartments a significant site of action for treating systemic lupus erythematosus and rheumatoid arthritis (Kuznik et al., 2011).

Other names

Endolysosomal systemMHC class II compartment (MIIC)Endocytic pathwayLysosomal-endosomal system

Inhibition of endosomal acidification and lysosomal protease activity, leading to impaired antigen processing and reduced Toll-like receptor signaling (Schrezenmeier & Dörner, 2020).