MHC Class I

Major Histocompatibility Complex (MHC) Class I molecules are a group of proteins found on the surface of all nucleated cells in the body. They play a crucial role in the immune system by presenting peptide fragments derived from the proteasome degradation of proteins within the cell to T cells. Specifically, they present these peptides to CD8+ T cells, also known as cytotoxic T lymphocytes (CTLs), which are responsible for the destruction of infected or dysfunctional cells.

Structure

MHC Class I molecules are composed of two chains: a larger α (alpha) chain that is encoded by the MHC gene, and a smaller β2-microglobulin (β2m) that is encoded by a gene outside the MHC locus. The α chain is anchored in the membrane and consists of three domains: α1, α2, and α3. The peptide-binding groove, where peptides are presented to T cells, is formed by the α1 and α2 domains. The α3 domain interacts with the CD8 molecule on T cells, stabilizing the interaction between the T cell and the antigen-presenting cell.

Function

The primary function of MHC Class I molecules is to alert the immune system to the presence of intracellular pathogens such as viruses or some bacteria, as well as to signal when a cell has become cancerous. They do this by presenting small peptides (8-10 amino acids in length) from the cell's internal proteins on the cell surface. When a cell is infected or becomes cancerous, the peptides presented by MHC Class I molecules are derived from these abnormal or foreign proteins, allowing CD8+ T cells to recognize and kill the affected cell.

Genetic Diversity

The genes encoding MHC Class I molecules are highly polymorphic, meaning there is a great variety in the sequence of these genes within the human population. This genetic diversity ensures that different individuals are able to present a wide range of peptides and respond to a wide range of pathogens. There are three main MHC Class I genes in humans, known as HLA-A, HLA-B, and HLA-C.

Pathway of Antigen Presentation

1. Proteins within the cell are degraded into peptides by the proteasome. 2. These peptides are transported into the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP). 3. In the ER, peptides are loaded onto MHC Class I molecules. 4. The peptide-MHC Class I complexes are then transported to the cell surface for presentation to CD8+ T cells.

Clinical Significance

MHC Class I molecules are involved in a number of clinical conditions. Their role in presenting viral peptides makes them crucial in the immune response to viral infections. Additionally, the variability in MHC Class I molecules among individuals contributes to the complexity of organ transplantation, as differences in MHC molecules between donor and recipient can lead to transplant rejection. Furthermore, certain HLA alleles are associated with increased or decreased susceptibility to various diseases, including autoimmune diseases.

See Also

• Immune system
• T cell
• MHC Class II
• Antigen presentation
• Autoimmune diseases
• Transplant rejection