The human leukocyte antigen (HLA) system is a collection of genes on chromosome 6 that encode proteins found on cell surfaces. These proteins help the immune system identify which cells belong to the body and which do not. HLA-DP is a component within this system that distinguishes between “self” and “non-self” elements. This distinction is fundamental for the immune system to defend against threats while avoiding harm to the body’s own tissues.
Understanding HLA-DP
HLA-DP is a Class II Major Histocompatibility Complex (MHC) molecule. It is a protein structure composed of two non-covalently linked chains, an alpha (DPA) and a beta (DPB) chain, anchored in the cell membrane. These molecules are primarily found on the surface of specialized immune cells called antigen-presenting cells (APCs), including B lymphocytes, macrophages, and dendritic cells.
The genes encoding both the alpha and beta chains of HLA-DP are polymorphic among individuals. This genetic diversity within HLA-DP contributes to the immune system’s capacity to recognize a wide range of foreign substances. The polymorphism is concentrated within the peptide-binding groove, the part of the molecule that holds antigen fragments. This variability allows for up to four different HLA-DP molecules to be expressed by an individual, each with distinct peptide-binding specificities.
The Immune Role of HLA-DP
The primary function of HLA-DP molecules is to present processed foreign peptides, or antigens, to T-helper cells (CD4+ T cells). This process, called antigen presentation, involves the uptake and breakdown of external proteins by antigen-presenting cells. After processing, fragments of these foreign proteins are loaded into the peptide-binding groove of the HLA-DP molecule.
Once loaded with an antigen fragment, the HLA-DP molecule displays it on the cell surface. T-helper cells then recognize and bind to this HLA-DP-peptide complex. This interaction activates other immune cells, including B cells to produce antibodies and cytotoxic T cells to eliminate infected cells. This ensures the immune system effectively targets and eliminates pathogens.
HLA-DP and Its Clinical Significance
Differences in HLA-DP types can lead to immune rejection in organ or tissue transplantation. When a donor’s HLA-DP molecules are not a close match to the recipient’s, the recipient’s immune system can perceive the transplanted organ as foreign and launch an attack. Therefore, HLA matching between donor and recipient is important for successful transplants and reducing organ rejection.
Specific HLA-DP variants are linked to susceptibility to certain autoimmune diseases. In these conditions, the immune system mistakenly recognizes the body’s own tissues as foreign, leading to self-attack.
HLA-DP also has a role in predicting severe adverse drug reactions. Certain HLA-DP alleles can predispose individuals to immune-mediated reactions to specific medications. Identifying these associations through genetic screening can help prevent delayed drug allergy reactions.