HLA-DPB1 : major histocompatibility complex, class II, DP beta 1

Description

The HLA-DPB1 (major histocompatibility complex, class II, DP beta 1) is a protein-coding gene located on chromosome 6.

The HLA-DPB1 gene provides instructions for making a protein that plays a critical role in the immune system. The HLA-DPB1 gene is part of a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria.The HLA complex is the human version of the major histocompatibility complex (MHC), a gene family that occurs in many species. The HLA-DPB1 gene belongs to a group of MHC genes called MHC class II. MHC class II genes provide instructions for making proteins that are present on the surface of certain immune system cells. These proteins attach to protein fragments (peptides) outside the cell. MHC class II proteins display these peptides to the immune system. If the immune system recognizes the peptides as foreign (such as viral or bacterial peptides), it triggers a response to attack the invading viruses or bacteria.The protein produced from the HLA-DPB1 gene attaches (binds) to the protein produced from another MHC class II gene, HLA-DPA1. Together, they form a functional protein complex called an antigen-binding DPαβ heterodimer. This complex displays foreign peptides to the immune system to trigger the body's immune response.Each MHC class II gene has many possible variations, allowing the immune system to react to a wide range of foreign invaders. Researchers have identified hundreds of different versions (alleles) of the HLA-DPB1 gene, each of which is given a particular number (such as HLA-DPB1*03:01).

The HLA-DPB1 gene codes for a protein that plays a critical role in the immune system by presenting antigens to CD4 T-cells. This protein binds to peptides derived from antigens that enter antigen-presenting cells (APCs) through the endocytic pathway. It then displays these peptides on the cell surface, allowing CD4 T-cells to recognize and respond to foreign invaders. This process is essential for the immune system to mount a targeted response against pathogens. The peptide binding cleft of HLA-DPB1 can accommodate peptides ranging from 10 to 30 amino acids in length. The peptides presented by HLA-DPB1 are generated through the breakdown of proteins that enter the endocytic pathway and are processed by lysosomal proteases. This process is often referred to as exogenous antigen presentation, as the antigens are derived from sources outside the cell. However, exogenous antigens must compete with endogenous peptides derived from normal cellular processes. Autophagy, a process that degrades cellular components, also contributes to the pool of endogenous peptides presented by HLA-DPB1. In addition to APCs, epithelial cells in the gastrointestinal tract also express HLA-DPB1, making them capable of presenting antigens to T-cells. This is a unique feature of the digestive system. To produce a functional MHC class II molecule for antigen presentation, three HLA-DPB1 molecules associate with a CD74 trimer in the endoplasmic reticulum (ER). This complex then enters the endocytic pathway, where CD74 undergoes sequential degradation, leaving behind a small fragment called CLIP. HLA-DM, another protein, binds to the HLA-DPB1-CLIP complex, facilitating the release of CLIP. HLA-DM then stabilizes the HLA-DPB1 molecule until it binds to a high-affinity antigenic peptide. This peptide-bound HLA-DPB1 molecule is then transported to the cell surface for presentation. In B-cells, the interaction between HLA-DM and HLA-DPB1 is regulated by HLA-DO. Primary dendritic cells (DCs) also express HLA-DO. The acidic environment of lysosomes plays a crucial role in regulating antigen loading onto HLA-DPB1 by enhancing proteolysis and facilitating efficient peptide binding.

HLA-DPB1 is also known as DPB1, HLA-DP, HLA-DP1B, HLA-DPB.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing