HLA-DQB1 : major histocompatibility complex, class II, DQ beta 1

Description

The HLA-DQB1 (major histocompatibility complex, class II, DQ beta 1) is a protein-coding gene located on chromosome 6.

The HLA-DQB1 gene provides instructions for making a protein that plays a critical role in the immune system. The HLA-DQB1 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-DQB1 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-DQB1 gene attaches (binds) to the protein produced from another MHC class II gene, HLA-DQA1. Together, they form a functional protein complex called an antigen-binding DQαβ 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-DQB1 gene, each of which is given a particular number (such as HLA-DQB1*06:02).

HLA-DQB1, a crucial component of the immune system, plays a role in recognizing foreign invaders. It binds to peptides derived from antigens that enter antigen-presenting cells (APCs) through the endocytic pathway. These peptides, ranging from 10 to 30 amino acids long, are presented on the cell surface for recognition by CD4 T-cells. The peptides presented by MHC class II molecules are predominantly generated through the degradation of proteins that enter the endocytic pathway, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens taken up by APCs are readily presented via MHC II molecules, thus this antigen presentation pathway is commonly referred to as exogenous. However, exogenous antigens must compete with those derived from endogenous components as membrane proteins destined for degradation in lysosomes are also present in the endosomal/lysosomal compartments. Autophagy also contributes to the pool of endogenous peptides, as autophagosomes fuse with MHC class II loading compartments. Beyond APCs, other cells in the gastrointestinal tract, such as epithelial cells, express MHC class II molecules, CD74, and act as APCs, which is unique to the GI tract. To produce an antigen-presenting MHC class II molecule, three MHC class II molecules (alpha-beta heterodimers) associate with a CD74 trimer in the endoplasmic reticulum (ER) to form a heterononamer. Upon entering the endosomal/lysosomal system, where antigen processing occurs, CD74 undergoes sequential degradation by proteases, leaving a small fragment known as CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM, which binds directly to the alpha-beta-CLIP complex, releasing CLIP. HLA-DM stabilizes MHC class II molecules until high-affinity antigenic peptides bind. The MHC II molecule bound to a peptide is then transported to the cell surface. In B-cells, the interaction between HLA-DM and MHC II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also express HLA-DO. The lysosomal microenvironment plays a role in regulating antigen loading into MHC II molecules; increased acidification leads to enhanced proteolysis and efficient peptide loading.

HLA-DQB1 is also known as CELIAC1, HLA-DQB, IDDM1.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing