Dendritic cell antigen processing and MHC class II presentation pathway (MHCII pathway)

The dendritic cell antigen processing and MHC class II presentation pathway is a fundamental mechanism of the adaptive immune system, enabling the detection of exogenous pathogens and the maintenance of self-tolerance (Unanue et al., 2016). This complex process involves the internalization of extracellular proteins via endocytosis or phagocytosis, followed by their degradation into short peptides within acidified endolysosomal compartments by proteases like cathepsins (Roche & Furuta, 2015). MHC class II molecules, synthesized in the endoplasmic reticulum and stabilized by the invariant chain (CD74), meet these peptides in the MIIC (MHC class II compartment), where the chaperone HLA-DM facilitates the exchange of the CLIP peptide for high-affinity antigenic fragments (Wieczorek et al., 2017). The resulting peptide-MHC II complexes are then trafficked to the plasma membrane for presentation to CD4+ T cells, providing the signal necessary for T-cell activation. Dysregulation of this pathway is central to the pathogenesis of autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, where self-antigens are inappropriately presented, and in cancer, where tumors may evade immune surveillance by downregulating MHC II components (Roche & Furuta, 2015). Pharmacological modulation of this pathway includes the use of antimalarials like hydroxychloroquine, which raises endosomal pH to impair antigen processing, and various immunotherapies designed to enhance dendritic cell function in the context of vaccination (Rainsford et al., 2015).

Other names

MHC class II exogenous pathwayEndocytic pathway of antigen presentationAntigen processing and presentation via MHC class IIExogenous antigen presentation pathway

Modulation of endosomal pH, inhibition of lysosomal proteases (cathepsins), downregulation of MHC class II expression, or interference with T-cell costimulation following presentation.