Major Histocompatibility Complex I- Structure, Mechanism, Functions


Major Histocompatibility Complex I (MHC I) is a type of molecule that plays a key role in presenting antigens to T cells and thus activating the adaptive immune system. MHC I molecules are expressed on the surface of almost all nucleated cells in the body, except for red blood cells, nervous tissues and platelets.

The structure of MHC I molecules consists of two polypeptide chains: a longer alpha chain (45 kDa) and a shorter beta-2 microglobulin chain (12 kDa). The alpha chain has three domains: alpha-1, alpha-2 and alpha-3. The alpha-1 and alpha-2 domains form a cleft that binds to a peptide antigen, while the alpha-3 domain anchors the molecule to the cell membrane. The beta-2 microglobulin chain is non-covalently attached to the alpha-3 domain and does not span the membrane.

The peptide-binding cleft of MHC I molecules can accommodate peptides of 8 to 10 amino acids in length. These peptides are derived from the degradation of endogenous proteins, such as viral or tumor antigens, by the proteasome in the cytoplasm. The peptides are then transported to the endoplasmic reticulum (ER) by a transporter associated with antigen processing (TAP), where they are loaded onto MHC I molecules with the help of other proteins, such as tapasin, calreticulin and ERp57. The loaded MHC I molecules then travel to the cell surface via the Golgi apparatus.

The structure of MHC I molecules allows them to present antigens to CD8+ T cells, also known as cytotoxic T cells. CD8+ T cells have receptors (TCRs) that recognize both the peptide antigen and the MHC I molecule on the target cell. When this recognition occurs, CD8+ T cells are activated and can induce apoptosis (programmed cell death) of the target cell. This mechanism is important for eliminating infected or transformed cells and mediating cellular immunity.

In humans, there are three main types of MHC I molecules: HLA-A, HLA-B and HLA-C. These molecules are highly polymorphic, meaning that there are many different variants (alleles) of each gene in the population. This diversity ensures that different individuals can present a wide range of antigens and mount an effective immune response against various pathogens. However, it also poses a challenge for organ transplantation, as mismatched MHC I molecules can trigger immune rejection by the recipient`s CD8+ T cells.