Antigen Processing and Presentation

Antigen processing and presentation are fundamental immunological processes that allow T cells to recognize foreign antigens, such as peptides from pathogens, and distinguish them from self-antigens. This recognition is only possible when the fragments are physically displayed on the cell surface by Major Histocompatibility Complex (MHC) molecules. There are two antigen presentation pathways, MHC Class I and MHC Class II, which present antigens, depending on whether the antigen originated inside or outside the cell. This determines which T cell subset will be activated. MHC Class II Pathway includes endogenous (Intracellular) antigens, such as viral proteins or tumor antigens. Exogenous (Extracellular) antigens, such as bacteria or toxins taken up by phagocytosis. The cells involved include: Professional Antigen-Presenting Cells (APCs), Dendritic Cells, Macrophages, B cells, CD8+ Cytotoxic T Cells, and CD4+ Helper T Cells. The MHC Class I Pathway (Endogenous) alerts CD8+ T cells to an intracellular threat so the cell can be destroyed. Proteins (self or foreign, e.g., viral) in the cytoplasm are tagged with ubiquitin and degraded into short peptides by the proteasome. The peptides are transported into the Endoplasmic Reticulum (ER) by the TAP (Transporter Associated with Antigen Processing) proteins. In the ER, an MHC Class I molecule is assembled and stabilized by chaperones. The short peptide binds to the groove of the MHC Class I molecule, displacing the chaperones. The stable peptide-MHC I complex travels through the Golgi apparatus and is expressed on the cell surface for inspection by CD8+ T cells. The MHC Class II Pathway (Exogenous) activates CD4+ T cells, which then coordinate the broader immune response. Professional APCs (Dendritic Cells, Macrophages, B cells) internalize extracellular antigens (e.g., bacteria) via phagocytosis or endocytosis, placing them inside a vesicle called an endosome. Proteases in the increasingly acidic endosome/lysosome compartment degrade the antigen into peptide fragments. Meanwhile, the MHC Class II molecule is synthesized in the ER and protected by an Invariant Chain (Ii), which prevents it from binding endogenous peptides. The MHC II-Ii complex is routed to the endosome. In the endosome, an enzyme (HLA-DM) removes a fragment of the invariant chain (CLIP), allowing the processed exogenous peptide to bind to the MHC Class II molecule's groove. The stable peptide-MHC II complex is transported to and displayed on the APC's surface for inspection by CD4+ T cells.