Human MHC class I and II antigen presentation pathways (MHC I/II pathways)

The Human MHC class I and II antigen presentation pathways are fundamental biological processes that enable the adaptive immune system to monitor the intracellular and extracellular environments for threats. The MHC class I pathway is present in almost all nucleated cells and presents endogenous peptides, derived from the cytosol via the proteasome and TAP transporter, to CD8+ cytotoxic T cells to identify virally infected or malignant cells [1, 4, 7]. The MHC class II pathway is primarily restricted to professional antigen-presenting cells (APCs) such as dendritic cells and macrophages, presenting exogenous peptides from the endocytic pathway to CD4+ helper T cells to coordinate immune responses [1, 4, 13]. These pathways are critical in oncology, where tumors often downregulate MHC expression to evade immune surveillance, and in autoimmune diseases, where the aberrant presentation of self-antigens leads to tissue damage [2, 6, 12, 15]. Therapeutic strategies include upregulating MHC expression with interferons to enhance anti-tumor immunity, using immunosuppressants like calcineurin inhibitors to modulate antigen processing in transplantation, and developing novel agonists like eftilagimod alfa that target MHC II to enhance APC activation [3, 10, 18].

Other names

HLA class I and II pathwaysAntigen processing and presentation pathwaysMajor Histocompatibility Complex pathwaysMHC-I and MHC-II antigen presentation pathways

Drugs targeting these pathways modulate the immune response by either inducing the expression of MHC molecules and their associated processing machinery (e.g., Interferon gamma), inhibiting the proteolytic generation or transport of antigenic peptides (e.g., Bortezomib, Cyclosporin A), or directly engaging MHC molecules to stimulate or inhibit immune cell activation (e.g., Eftilagimod alfa) [3, 6, 10, 18].