Human Leukocyte Antigen class I (HLA-I) is a set of proteins found on the surface of nearly every cell in the human body. These molecules function as part of the immune system’s surveillance mechanism. They act like cellular identification cards, displaying information to patrolling immune cells, which allows the immune system to differentiate healthy cells from those that are unhealthy or foreign.
The genes that encode for HLA proteins are located on chromosome 6. These proteins are a component of the major histocompatibility complex (MHC), a system found in many animals. In humans, these are specifically referred to as HLA.
The Cellular Billboard System
The surface of each cell acts as a communication hub, with HLA-I molecules serving as miniature billboards. These structures continuously display fragments of proteins from within the cell’s internal environment. This process begins when proteins inside the cell are broken down into smaller pieces called peptides, often consisting of about 8-10 amino acids.
HLA-I molecules bind with these peptides deep within the cell. This complex then transports the peptide fragment to the cell’s outer surface, embedding it within the cell membrane for presentation. This external surveillance is a constant process, ensuring that any changes in a cell’s protein production are quickly advertised.
Role in Fighting Infections and Cancer
This cellular display system is fundamental to the body’s defense against internal threats like viruses and malignancies. When a virus infects a cell, it hijacks the cell’s machinery to produce its own viral proteins. These foreign proteins are processed and presented on the cell’s surface by HLA-I molecules.
Specialized immune cells, known as cytotoxic T cells, constantly patrol the body, examining the peptides presented by HLA-I molecules. When a T cell encounters a foreign peptide, it recognizes the cell as infected and triggers the cell’s destruction, thereby halting the spread of the virus.
A similar process occurs with cancer cells. Cancer arises from genetic mutations that can lead to the production of abnormal proteins. These altered proteins can also be presented on the cell surface via the HLA-I system, flagging the cancerous cell as abnormal and allowing cytotoxic T cells to identify and eliminate it.
Importance in Medical Procedures
The unique nature of an individual’s HLA molecules is a factor in medical procedures such as organ and tissue transplantation. Because the HLA system is specific to each person, a recipient’s immune system will almost always identify a donor organ’s cells as foreign. This mismatch can trigger an immune response known as transplant rejection. To minimize this risk, physicians perform HLA matching to find a donor whose HLA molecules are as similar as possible to the recipient’s, improving the long-term success of the transplant.
This principle is also important in bone marrow transplantation. A close HLA match is necessary to prevent the donor’s immune cells from attacking the recipient’s tissues, a condition known as graft-versus-host disease.
Connection to Autoimmune Disorders
The HLA-I system’s ability to distinguish self from non-self is not infallible and its malfunction is associated with autoimmune disorders. In these conditions, the immune system mistakenly attacks the body’s own healthy tissues. Certain variations of HLA genes are strongly linked to an increased risk for developing specific autoimmune diseases.
These particular HLA-I molecules may present the body’s own “self-peptides” in a way that provokes a response from immune cells, leading it to identify normal body proteins as threats. A well-known example is the association between the HLA-B27 allele and ankylosing spondylitis, an inflammatory arthritis that primarily affects the spine. Individuals who carry the HLA-B27 gene have a significantly higher risk of developing the disease because the molecule’s presentation of peptides can lead to an erroneous immune attack on the joints.
Genetic Diversity and HLA Typing
The genes responsible for the HLA system are the most varied, or polymorphic, in the human genome, with thousands of different versions, known as alleles. This diversity is an evolutionary advantage for the human species. It makes it difficult for a single pathogen to evolve in a way that allows it to evade the immune systems of an entire population. This genetic variability ensures that within any group of people, there will be a wide range of HLA molecules capable of presenting fragments from a new pathogen.
To identify an individual’s specific set of HLA genes, laboratories perform a test called HLA typing. This analysis determines which specific HLA alleles a person has inherited.