MHCIWeg

MHCIWeg refers to the MHC class I antigen presentation pathway. It is the cellular process by which intracellular proteins are degraded into peptides, which are loaded onto MHC class I molecules and transported to the cell surface to be recognized by CD8+ T cells. The pathway primarily handles endogenous antigens and is central to immune surveillance of infected or malignant cells. Most nucleated cells express MHC I, while professional antigen-presenting cells also use MHC I to activate CD8+ T cells and to cross-present exogenous antigens in some contexts.

Process overview: Cytosolic proteins are degraded by the proteasome into short peptides. In inflammatory conditions, immunoproteasomes alter peptide production. Peptides are transported into the endoplasmic reticulum via the transporter associated with antigen processing (TAP1 and TAP2). In the ER, a peptide-loading complex coordinates association of the MHC class I heavy chain with beta-2 microglobulin, aided by calreticulin, ERp57, and tapasin. Peptide trimming by ERAAP can refine the length for optimal binding. Peptides that bind stabilise MHC I molecules, which then traffic through the Golgi to the cell surface as peptide–MHC I complexes.

Function and regulation: Surface MHC I–peptide complexes present endogenous epitopes to CD8+ T cells, enabling cytotoxic responses against infected or transformed cells. Cytokines such as IFN-γ upregulate pathway components, increasing antigen presentation. Evasion by pathogens and tumors can involve downregulation of TAP or proteasome subunits. Defects in the pathway (for example TAP deficiency) lead to impaired CD8+ T cell immunity.