Tumor antigen presentation via major histocompatibility complex class I and II pathway (MHC class I/II antigen presentation pathway)

The major histocompatibility complex (MHC) class I and II pathways are central mechanisms by which cells present antigens—including those derived from intracellular pathogens or mutated proteins—to immune effector cells. The process involves several steps: generation and trimming of peptides from cellular proteins by proteasomes (especially immunoproteasomes for optimal epitope generation), transport into the endoplasmic reticulum by specialized transporters like TAP for MHC-I peptides, loading onto nascent MHC molecules with assistance from chaperones such as tapasin and calnexin/carletriculin complexes, followed by surface expression where they can be recognized by CD8+ cytotoxic T lymphocytes. For exogenous antigens taken up through endocytosis/phagocytosis—such as those from extracellular bacteria—antigens are processed within endosomes before being loaded onto newly synthesized MHC-II molecules with help from invariant chain removal facilitated by HLA-DO/DM chaperones. The resulting complexes then migrate to the plasma membrane where they activate CD4+ helper T lymphocytes.[1][2][3] Defects in these pathways allow cancers to evade immune detection but also provide opportunities for therapeutic intervention aimed at restoring proper function so that tumors become visible again to host immunity.[1]

Other names

Major histocompatibility complex class I and II antigen processing and presentation machineryMHC-I/MHC-II APMHLA (human leukocyte antigen) class I/II pathway (in humans)Antigen processing and presenting machinery (APM)

Enhancement of tumor-specific peptide-MHC expression on cancer cells; restoration of defective APM function; stimulation of CD8+ cytotoxic T cell responses via improved endogenous peptide-MHC-I display; stimulation of CD4+ helper T cell responses via exogenous peptide-MHC-II display. Note: Direct modulation is rare. Most strategies aim to restore or enhance natural function rather than inhibit it.