- Human Leukocyte Antigen (HLA), also known as the Major Histocompatibility Complex (MHC) in humans, is a complex gene system crucial for immune recognition and response. These molecules are essential for distinguishing self from non-self and presenting antigens to immune cells. The HLA system is highly polymorphic, meaning there are many genetic variants in the population, which helps ensure population-wide resistance to pathogens. These genes are inherited as haplotypes and show codominant expression, with both parental alleles being expressed.
- The HLA system is divided into three main classes. HLA Class I molecules (A, B, C) are present on almost all nucleated cells and present peptides from intracellular proteins to CD8+ T cells. These molecules are crucial for viral infection recognition, tumor surveillance, and transplant rejection. They also serve as ligands for Natural Killer cells, playing a vital role in innate immunity. The widespread distribution of Class I molecules ensures that virtually any infected cell can signal its compromised state to the immune system.
- HLA Class II molecules (DP, DQ, DR) are primarily expressed on professional antigen-presenting cells, such as dendritic cells, macrophages, and B cells. They present peptides derived from extracellular proteins to CD4+ T helper cells, initiating and coordinating immune responses. Class II molecules are particularly important in the development of helper T cell responses and play significant roles in autoimmune diseases. The restricted expression of Class II molecules to professional antigen-presenting cells helps maintain controlled immune responses.
- HLA Class III genes, located between Class I and II genes, encode various immune system components, including complement proteins and cytokines like TNF-α and TNF-β. This region also contains genes for heat shock proteins and other molecules involved in inflammation. Although structurally different from Class I and II molecules, Class III products are equally important for immune function and inflammation regulation.
- The HLA system has profound clinical implications. It is central to organ and tissue transplantation, where matching HLA types between donor and recipient significantly improves transplant success. Various HLA alleles are associated with susceptibility or resistance to different diseases, particularly autoimmune conditions. Understanding HLA typing is also important for predicting vaccine responses and disease outcomes. The system’s extreme polymorphism and complex inheritance patterns make it both a fascinating subject of study and a challenging clinical consideration.
