MHCherkenning

MHCherkenning, often referred to as MHC recognition, describes how the immune system detects antigens by presenting peptide fragments on the surface of cells via major histocompatibility complex (MHC) molecules. This process enables T cells to discriminate self from non-self and to respond to infections or abnormal cells. There are two main classes of MHC molecules involved in antigen presentation: MHC class I and MHC class II.

MHC class I molecules are found on almost all nucleated cells. They present endogenous peptides, typically derived from proteins synthesized inside the cell, to CD8+ T cells. The peptide-binding groove is formed by the alpha chains, and a light chain called beta-2-microglobulin associates with them. Peptides are loaded in the endoplasmic reticulum with the help of the peptide-loading complex, which includes transporters associated with antigen processing (TAP), calreticulin, calnexin, ERp57, and tapasin. Once loaded, the peptide-MHC I complex travels to the cell surface. This pathway is also involved in cross-presentation, where extracellular antigens are presented on MHC I to activate CD8+ T cells.

MHC class II molecules primarily present exogenous peptides to CD4+ T helper cells. They are expressed mainly on professional antigen-presenting cells such as dendritic cells, macrophages, and B cells. Invariant chain blocks the peptide-binding groove in the endoplasmic reticulum, and subsequent removal leaves a CLIP fragment that is exchanged for high-affinity peptides by HLA-DM in endosomal/lysosomal compartments. This enables presentation of extracellular antigens to helper T cells, promoting B cell activation and cytokine responses.

Genetic polymorphism in MHC genes creates a broad range of peptide-binding repertoires, influencing immune responses, transplantation compatibility, and susceptibility to autoimmune diseases. In humans, MHC corresponds to HLA genes.