The human leukocyte antigen (HLA) system is a complex group of genes found on chromosome 6 in humans. These genes produce proteins located on the surface of most cells in the body. The HLA system plays a role in the immune system’s ability to distinguish between the body’s own cells and foreign invaders. Understanding these proteins helps in comprehending immune responses and various medical conditions.
What are HLA Proteins
HLA, or Human Leukocyte Antigens, are proteins found on the surface of most human cells. They are the human version of the Major Histocompatibility Complex (MHC), a gene family found in many animals. HLA proteins act like unique identification tags for the body’s cells, allowing the immune system to recognize them as “self.” The HLA gene complex is highly diverse, with many different forms (alleles) existing among individuals. This diversity helps the immune system adapt and respond to a wide range of potential threats.
How HLA Proteins Function
The primary function of HLA proteins involves antigen presentation, displaying peptides or antigens on the cell surface. These antigens are then presented to T cells, a type of white blood cell crucial for immune responses. This presentation allows T cells to survey cells and determine if they are healthy, infected, or abnormal. If a T cell recognizes a foreign or abnormal antigen presented by an HLA molecule, it can trigger an immune response to eliminate the affected cell or pathogen. This mechanism allows the immune system to differentiate between the body’s own components and potentially harmful foreign substances or diseased cells.
Types of HLA Proteins
HLA proteins are categorized into two classes: Class I and Class II, each with distinct locations and functions. HLA Class I molecules are found on the surface of almost all nucleated cells in the body, including HLA-A, HLA-B, and HLA-C. These Class I molecules primarily present peptides that originate from inside the cell, such as fragments of viral proteins if the cell is infected, or proteins from cancerous cells. This presentation allows cytotoxic T cells (CD8+ T cells) to identify and destroy infected or abnormal cells.
In contrast, HLA Class II molecules are found on specialized immune cells, antigen-presenting cells (APCs), including B cells, macrophages, and dendritic cells. These molecules, including HLA-DR, HLA-DQ, and HLA-DP, present antigens that originate from outside the cell. When an immune cell engulfs a bacterium, fragments of that bacterium are processed and presented by Class II HLA molecules to helper T cells (CD4+ T cells). This interaction activates the broader immune response, leading to the production of antibodies and coordination of immune cells to combat foreign invaders.
Importance in Health and Disease
HLA proteins have implications for various aspects of health, particularly in organ and tissue transplantation. Differences in HLA types between a donor and recipient can cause the recipient’s immune system to recognize the transplanted organ as foreign, leading to graft rejection. Matching HLA types between donor and recipient is therefore a primary consideration to improve transplant success rates and reduce rejection. Better survival rates are observed for recipients with HLA-matched organs.
Beyond transplantation, specific HLA types are associated with susceptibility or resistance to certain infectious diseases, influencing immune response to pathogens. Additionally, HLA genes are linked to a range of autoimmune conditions, where the immune system mistakenly attacks the body’s own healthy tissues. Examples include celiac disease, rheumatoid arthritis, and type 1 diabetes, where particular HLA alleles can increase the risk of developing these conditions. This connection shows the balance HLA proteins maintain in immune recognition.
HLA Typing and Its Significance
HLA typing identifies an individual’s specific HLA genes and proteins. This process is also known as histocompatibility testing. The primary application of HLA typing is in finding suitable donors for organ, tissue, or bone marrow transplants. A close HLA match between donor and recipient reduces transplant rejection and improves long-term success.
The testing involves analyzing blood or cheek swab samples to determine the unique HLA markers. HLA typing is also used for paternity testing or investigating associations between specific HLA types and diseases. For instance, the presence of HLA-B27 is associated with conditions like ankylosing spondylitis. This genetic information helps medical professionals make informed decisions for patient care and research.