Major Histocompatibility Complex (MHC) molecules are proteins located on the surface of cells throughout the body. These molecules serve as unique identifiers, allowing the immune system to distinguish between the body’s own cells and foreign invaders. They act much like an identification badge, constantly displaying information about the cell’s internal state. This continuous display is fundamental for maintaining immune surveillance and recognizing potential threats.
What MHC Molecules Are
MHC molecules are proteins embedded in the cell membrane. They function as display platforms, presenting small protein fragments, called antigens, on the cell’s outer surface. These antigens are derived from larger proteins broken down inside the cell. The MHC molecule holds a specific antigen within a groove, making it accessible for inspection by immune cells.
Cells constantly break down proteins and display fragments via MHC molecules, allowing the immune system to monitor their health. If a cell becomes infected or cancerous, it may produce unusual proteins. Fragments of these altered proteins are also presented by MHC molecules, signaling a change in the cell’s status to the immune system.
The Two Main Types and Their Distinct Roles in Antigen Presentation
The immune system utilizes two primary classes of MHC molecules, each with a specialized role in antigen presentation.
MHC Class I Molecules
MHC Class I molecules are found on the surface of nearly all nucleated cells. Their primary function involves presenting small protein fragments that originate from inside the cell, referred to as endogenous antigens. These internal antigens can be normal cellular components or fragments from viruses replicating within the cell or abnormal proteins produced by cancerous cells.
MHC Class I molecules present these internal antigens to cytotoxic T lymphocytes (CD8+ T cells). If a CD8+ T cell recognizes a viral or cancerous antigen presented by an MHC Class I molecule, it signals that the cell is infected or abnormal. This recognition triggers a response aimed at eliminating the compromised cell, preventing further spread of infection or disease.
MHC Class II Molecules
MHC Class II molecules are primarily located on the surface of specialized immune cells known as antigen-presenting cells (APCs). Examples of these professional APCs include macrophages, dendritic cells, and B lymphocytes. Their role involves presenting protein fragments that originate from outside the cell, known as exogenous antigens. These external antigens are typically derived from pathogens like bacteria or fungi that have been engulfed and processed by the APC.
Once an APC takes in an external pathogen, it breaks down the pathogen’s proteins into smaller fragments. These fragments are then loaded onto MHC Class II molecules and displayed on the cell surface. MHC Class II molecules present these exogenous antigens to helper T lymphocytes (CD4+ T cells). The interaction between the MHC Class II molecule presenting an antigen and the CD4+ T cell is a fundamental step in initiating a broader immune response against extracellular threats.
MHC’s Role in Immune System Activation
Antigen presentation by MHC molecules is a precise communication mechanism that initiates specific immune responses. T cells, a type of white blood cell, have specialized receptors that “read” antigen fragments displayed by MHC molecules. This interaction determines if an immune response is warranted. If an MHC molecule presents a fragment of a normal, “self” protein, the T cell recognizes it as harmless and does not react.
When an MHC molecule displays a “non-self” antigen, such as a piece of a viral protein or a bacterial component, the T cell’s receptor recognizes this as a foreign or dangerous signal. This recognition event activates the T cell, initiating a cascade of immune responses. Activated CD8+ T cells, which recognize antigens presented by MHC Class I, directly target and destroy infected or cancerous cells.
Activated CD4+ T cells, which recognize antigens presented by MHC Class II, do not directly kill cells but instead orchestrate other immune cells. They release signaling molecules that help activate B cells to produce antibodies or enhance the killing functions of macrophages. This coordinated response ensures that the immune system effectively combats a wide range of pathogens and cellular abnormalities.
Why MHC Diversity Matters
The genes encoding MHC molecules are highly diverse within the human population. This diversity arises from two main factors: MHC genes are “polygenic,” meaning multiple distinct genes contribute to the different types of MHC molecules an individual expresses. These genes are also “polymorphic,” meaning many different versions, or alleles, of each MHC gene exist among individuals. For example, thousands of human MHC gene alleles are known.
This genetic variability in MHC molecules across the human population serves an evolutionary purpose. It ensures that a population can recognize and mount an immune response against a vast array of pathogens. If one individual’s MHC molecules are unable to present a particular pathogen’s antigens, another individual with different MHC alleles might be able to, protecting the species.
The unique MHC profile of each person also has significant medical implications. In organ transplantation, a mismatch between donor and recipient MHC molecules can lead to transplant rejection because the recipient’s immune system identifies the transplanted organ as foreign. Additionally, certain MHC alleles are associated with increased susceptibility or resistance to autoimmune diseases, where the immune system mistakenly attacks the body’s own tissues.