Human Leukocyte Antigens (HLA) are proteins found on the surface of most cells in the human body. These proteins play a fundamental role in the body’s immune system, helping it distinguish between its own healthy cells (“self”) and foreign invaders (“non-self”), such as bacteria, viruses, or other abnormal cells. The unique combination of an individual’s HLA proteins contributes significantly to their biological individuality and how their body defends against disease.
Understanding Human Leukocyte Antigens (HLA)
HLA proteins are located on the surface of nearly all nucleated cells in the body, acting as molecular signposts. Their primary function involves presenting small fragments of proteins, known as antigens, to specialized immune cells called T-cells. This presentation allows the immune system to survey the internal environment of cells and identify potential threats.
These proteins are encoded by a cluster of genes situated within the Major Histocompatibility Complex (MHC) region on chromosome 6. There are two main classes of HLA molecules: Class I and Class II. Class I HLA molecules (HLA-A, HLA-B, and HLA-C) are expressed on the surface of almost all nucleated cells and present antigens derived from inside the cell. Class II HLA molecules (HLA-DR, HLA-DQ, and HLA-DP) are primarily found on certain immune cells, such as B lymphocytes, macrophages, and dendritic cells, and they present antigens acquired from outside the cell.
The Genetics of HLA Inheritance
HLA genes are notable for their high degree of “polymorphism,” meaning there are numerous different versions, or alleles, for each gene within the human population. This extensive variation contributes to the unique HLA profile of nearly every individual.
HLA genes are inherited in blocks called “haplotypes,” with each person receiving one haplotype from their mother and one from their father. This co-dominant inheritance pattern means that both paternal and maternal HLA genes are expressed simultaneously, further increasing an individual’s immune diversity. Siblings who share the same parents have a 25% chance of inheriting the exact same two haplotypes, making them a full HLA match. There is a 50% chance of siblings sharing one haplotype (a half-match) and a 25% chance of sharing no haplotypes at all.
HLA’s Role in Immune System Function
HLA proteins are fundamental for the immune system’s ability to differentiate between healthy body cells and foreign or abnormal cells. They function by presenting small peptide fragments to T-cells, effectively “showing” the immune system what is present inside or outside the cell. If a cell is infected by a virus, for example, Class I HLA molecules present fragments of the viral proteins, signaling to cytotoxic T-cells that the cell needs to be eliminated.
Variations in HLA types can influence an individual’s susceptibility or resistance to various diseases. Certain HLA alleles are associated with an increased risk of developing autoimmune conditions, where the immune system mistakenly attacks the body’s own tissues. HLA variations also play a role in how individuals respond to infectious diseases, with some alleles offering protection and others increasing susceptibility.
HLA Matching for Organ and Tissue Transplantation
HLA matching is an important aspect for the success of organ and tissue transplantation, such as kidney or bone marrow transplants. A close HLA match between a donor and recipient helps minimize the risk of the recipient’s immune system recognizing the transplanted organ as “non-self” and launching an immune attack, a process known as rejection. The degree of HLA mismatch directly correlates with the risk of both immediate (acute) and long-term (chronic) rejection.
Before a transplant, a process called HLA typing, or tissue typing, is performed to identify the specific HLA proteins of both the donor and recipient. This testing assesses compatibility, with particular attention paid to HLA-A, HLA-B, and HLA-DR loci, as mismatches in these areas can significantly increase rejection risk. Finding a perfect HLA match is often difficult due to the extensive diversity of HLA types in the human population. Despite these challenges, advancements in HLA typing technologies continue to improve the precision of matching and transplant outcomes.