Autophagy-dependent MHC class II (MHC-II) antigen presentation machinery

The Autophagy-dependent MHC class II (MHC-II) antigen presentation machinery is a complex cellular system that facilitates the delivery of intracellular antigens to the MHC-II pathway for presentation to CD4+ T cells (Münz, 2012, Frontiers in Immunology). Traditionally, MHC-II molecules are dedicated to presenting exogenous antigens, but this machinery allows for the processing of endogenous proteins, including viral and self-antigens, via macroautophagy (Schmid et al., 2007, Immunity). The process involves the sequestration of cytoplasmic components into autophagosomes, which then fuse with MHC-II-loading compartments (MIICs) where peptides are loaded onto MHC-II dimers (Crotzer & Blum, 2009, Journal of Immunology). This pathway plays a vital role in immune surveillance and the maintenance of self-tolerance, and its dysfunction is implicated in autoimmune diseases and the evasion of anti-tumor immunity (Zhou et al., 2005, Nature). Therapeutic modulation of this machinery is currently achieved through non-specific agents such as hydroxychloroquine, which blocks lysosomal degradation, or mTOR inhibitors like rapamycin, which stimulate autophagic flux (Levine & Kroemer, 2019, Cell).

Other names

Autophagy-mediated MHC II presentationMacroautophagy-dependent MHC II antigen processingEndogenous MHC II presentation pathway

Modulation of autophagic flux and lysosomal degradation to alter the repertoire of antigens presented on MHC class II molecules.