Major Histocompatibility Complex (MHC) Class I molecules are proteins central to the immune system. They function as a cellular surveillance system, constantly presenting fragments of proteins from inside a cell on its surface. This display allows the immune system to monitor cells, identifying and responding to threats. Their widespread presence on almost all nucleated cells underscores their importance in maintaining cellular health and overall immune defense.
Cellular Identity Markers
MHC Class I molecules are complex structures composed of two main parts: a heavy chain (also known as an alpha-chain) and a smaller, non-covalently associated light chain called beta-2 microglobulin. The heavy chain features three extracellular domains, a transmembrane region, and a cytoplasmic tail. The peptide-binding groove, which holds protein fragments, is located between the alpha1 and alpha2 domains of the heavy chain.
These molecules are found on the surface of nearly all nucleated cells. They act like unique “cellular ID tags,” displaying small pieces of proteins that are normally present within healthy cells. This continuous presentation of “self” peptides allows the immune system to recognize and distinguish healthy cells from those that might be compromised.
Presenting Internal Threats
MHC Class I molecules present protein fragments, or peptides, from within the cell on the cell surface. Cellular proteins, including both normal “self” proteins and abnormal proteins, are continuously broken down into smaller peptides by a cellular machinery called the proteasome. This process is part of regular protein turnover within the cell.
These peptides are then transported into the endoplasmic reticulum. There, these peptides are loaded onto newly synthesized MHC Class I molecules. Once loaded, the MHC Class I-peptide complexes are transported to the cell surface, where they are displayed for immune surveillance. This continuous display allows the immune system to sample the internal protein content of cells.
MHC Class I and Immune Defense
MHC Class I molecules initiate specific immune responses. Specialized immune cells called cytotoxic T lymphocytes, also known as killer T cells or CD8+ T cells, constantly survey the peptides presented by MHC Class I molecules on cell surfaces. These T cells possess receptors that can recognize specific peptide-MHC Class I complexes.
If a killer T cell encounters an “abnormal” peptide presented by an MHC Class I molecule, which could indicate a viral infection or cancerous transformation, it activates the killer T cell, prompting it to eliminate the compromised cell. This targeted destruction prevents the spread of infection by destroying virus-infected cells and controls tumor growth by eliminating cancerous cells.
Beyond Infection Broader Implications
Beyond fighting infections and cancer, MHC Class I molecules have broader implications, particularly in organ transplantation. These molecules are also known as Human Leukocyte Antigens (HLAs) in humans, with types like HLA-A, HLA-B, and HLA-C. Differences in HLA types between a donor and a recipient can lead to the recipient’s immune system recognizing the transplanted organ as foreign, resulting in transplant rejection.
HLA matching between donor and recipient is a routine step before organ transplantation to minimize rejection risk. Some pathogens, such as certain viruses, and even cancer cells, have evolved mechanisms to interfere with MHC Class I expression or function. By altering MHC Class I display, these cells evade detection and elimination by killer T cells, allowing the infection or tumor to persist.