MHC class I

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MHC Class I processing

Major Histocompatibility Complex (MHC) Class I molecules are a group of proteins found on the cell surfaces 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 cells. This process is vital for the immune response to infected or malignant cells, as it allows the immune system to recognize and eliminate cells that are not functioning correctly.

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 cell membrane, and it is this complex of the α chain with β2m that forms the functional MHC Class I molecule on the cell surface. The α chain is divided into three domains: α1, α2, and α3. The peptide-binding groove, which holds the peptide to be presented to T cells, is formed by the α1 and α2 domains.

Function

The primary function of MHC Class I molecules is to display peptide fragments of proteins from within the cell to CD8+ T cells. This process begins when intracellular proteins are degraded by the proteasome into smaller peptides. These peptides are then transported into the endoplasmic reticulum by the transporter associated with antigen processing (TAP). In the endoplasmic reticulum, peptides that have the appropriate length and sequence are loaded onto MHC Class I molecules. The MHC Class I-peptide complex is then transported to the cell surface, where it can be recognized by the T cell receptor (TCR) on CD8+ T cells.

If the peptide presented by the MHC Class I molecule is recognized as foreign, such as in the case of a viral infection or a mutated cancer cell, the CD8+ T cell will initiate a response that can lead to the destruction of the infected or malignant cell. This is a critical mechanism of the immune system for controlling infections and preventing the spread of cancer.

Genetic Diversity

The genes encoding MHC Class I molecules are highly polymorphic, meaning there is a great deal of variation in the MHC Class I genes within the population. This genetic diversity ensures that the population as a whole can present a wide range of peptides and respond to a wide variety of pathogens. However, it also means that individuals vary in their response to infections and their susceptibility to certain diseases.

Clinical Significance

MHC Class I molecules are involved in several clinical conditions. Their role in presenting viral peptides makes them central in the immune response to viral infections. They are also involved in transplant rejection, as the immune system can recognize MHC molecules from a different individual as foreign and initiate an immune response against the transplanted tissue. Additionally, certain MHC Class I alleles are associated with an increased or decreased risk of autoimmune diseases and cancer.

See Also

• Immune system
• T cell
• MHC class II
• Transplant rejection
• Autoimmune disease