Major Histocompatibility Complex class II antigen processing and presentation pathway (MHC II pathway)

The MHC class II antigen processing and presentation pathway is a fundamental immunological process by which professional antigen-presenting cells (APCs), such as dendritic cells, macrophages, and B cells, internalize exogenous proteins and present their peptide fragments to CD4+ T helper cells (immunology.org, nih.gov). This pathway begins with the endocytosis or phagocytosis of extracellular antigens, which are then degraded into peptides by lysosomal proteases like cathepsins within acidic endosomal compartments (microbenotes.com, wikipedia.org). Concurrently, MHC class II molecules (HLA-DR, -DQ, -DP) are synthesized in the endoplasmic reticulum and stabilized by the invariant chain (Ii), which prevents premature peptide binding and directs the complex to the endocytic pathway (reactome.org, nih.gov). In the late endosomes, Ii is proteolytically cleaved to leave the CLIP fragment, which is subsequently exchanged for an antigenic peptide with the help of the chaperone HLA-DM (lifeandbiology.com, nih.gov). The resulting peptide-MHC II complex is transported to the cell surface to initiate adaptive immune responses or maintain peripheral tolerance (nih.gov, researchgate.net). Dysregulation of this pathway is central to the pathogenesis of autoimmune diseases, where self-peptides are inappropriately presented, and in cancer, where tumors may downregulate MHC II to evade immune surveillance (nih.gov, ovid.com).

Other names

MHCII pathwayExogenous antigen presentation pathwayHLA class II pathwayMHC class II presentation

Modulation of endosomal pH, inhibition of lysosomal proteolysis, blockade of peptide loading, or inhibition of MHC-II expression