Antigenpresentation

Antigen presentation is the process by which cells display peptide fragments bound to major histocompatibility complex (MHC) molecules on their surface, enabling T cells to monitor for signs of infection or dysregulation. Effective antigen presentation requires specialized antigen-presenting cells and the appropriate co-stimulatory signals to activate T cells and initiate an adaptive immune response.

MHC class I molecules present endogenous peptides, derived from proteins synthesized within the cell, to CD8+ cytotoxic T cells. Intracellular proteins are degraded by the proteasome, the resulting peptides are transported into the endoplasmic reticulum by TAP transporters, where they are loaded onto MHC I with the help of chaperones such as calnexin and tapasin. The peptide–MHC I complex is then transported to the cell surface for recognition by CD8+ T cells, which may trigger cytotoxic responses.

MHC class II molecules present exogenous peptides, derived from proteins taken up by endocytosis or phagocytosis, to CD4+ helper T cells. Antigenic proteins are degraded in endosomal/lysosomal compartments; MHC II heavy and light chains are synthesized in the ER and associate with the invariant chain, which blocks peptide binding and directs trafficking to endosomes. In endosomes, the invariant chain is removed by proteases and HLA-DM facilitates loading of peptides onto MHC II, which then travels to the cell surface.

Professional antigen-presenting cells—such as dendritic cells, macrophages, and B cells—are specialized for antigen presentation and provide necessary co-stimulatory signals. Some non-professional cells can present antigen via MHC I, particularly during inflammation or infection, but they usually lack robust co-stimulatory capacity.

Cross-presentation allows certain dendritic cells to present extracellular antigens on MHC I to CD8+ T cells, linking humoral and cellular immunity. Antigen presentation is central to immune surveillance, vaccine design, and cancer immunotherapy, influencing how effectively the immune system detects and responds to pathogens and diseased cells.