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  3. HLA-DPB1

HLA-DPB1 (Major histocompatibility complex, class II, DP beta 1)

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Summary of HLA-DPB1

This gene encodes a protein that helps the body recognize pathogens and let the immune system fight against them. It is associated with arthritis (R).

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The Function of HLA-DPB1

Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route, where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules, and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments, exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides, autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs, other cells of the gastrointestinal tract, such as epithelial cells, express MHC class II molecules and CD74 and act as APCs, which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen, three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs, CD74 undergoes a sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells, the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules, increased acidification produces increased proteolysis and efficient peptide loading.

Protein names

Recommended name:

HLA class II histocompatibility antigen, DP beta 1 chain

Alternative name(s):

HLA class II histocompatibility antigen, DP(W4
MHC class II antigen DPB1

HLA-DPB1 SNPs

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  1. RS1042151 (HLA-DPB1) ??
  2. RS2281388 (HLA-DPB1) ??
  3. RS3117242 (HLA-DPB1) ??
  4. RS4282438 (HLA-DPB1) ??
  5. RS6928954 (HLA-DPB1) ??
  6. RS7756516 (HLA-DPB1) ??
  7. RS9276370 (HLA-DPB1) ??
  8. RS9277535 (HLA-DPB1) ??
  9. RS9277554 (HLA-DPB1) ??
  10. RS9277555 (HLA-DPB1) ??
  11. RS9366816 (HLA-DPB1) ??

Top Gene-Substance Interactions

HLA-DPB1 Interacts with These Diseases

Disease Score

Substances That Increase HLA-DPB1

Substances Interaction Organism Category

Substances That Decrease HLA-DPB1

Substances Interaction Organism Category

Advanced Summary

     granulomatosis with polyangiitis At least one variant of the HLA-DPB1 gene has been associated with granulomatosis with polyangiitis (GPA). This condition occurs when the immune system malfunctions and attacks the body's own tissues and organs (autoimmunity), causing inflammation that affects the lungs, airways, and kidneys. The associated variant, called HLA-DPB1*0401, has been found more frequently in people with GPA than in those who do not have the condition; this variant is thought to increase the risk of developing GPA. Because the HLA-DPB1 gene is involved in the immune system, changes in it might be related to the autoimmune response and inflammation that damage the lungs, kidneys, and other organs. However, it is unclear what specific role the HLA-DPB1 gene variant plays in development of this condition. It is likely that environmental factors trigger the condition in people who are genetically predisposed to it. Other genetic factors are also likely to be involved in GPA. juvenile idiopathic arthritis Genetics Home Reference provides information about juvenile idiopathic arthritis. rheumatoid arthritis Genetics Home Reference provides information about rheumatoid arthritis. other disorders Variants of the HLA-DPB1 gene are associated with immune reactions to beryllium, a metallic element that can be toxic. Beryllium exposure can occur in manufacturing plants and the nuclear and aerospace industries. About 2 to 10 percent of people exposed to beryllium develop beryllium sensitization or chronic beryllium disease. Sensitization is an immune reaction that occurs in response to beryllium exposure; sensitization can cause an increase in the number of certain immune system cells in the blood, but it may not lead to any symptoms. In some people, sensitization leads to chronic beryllium disease, which is a lung disease characterized by the formation of small masses of inflammatory cells (granulomas). The lungs can become scarred and stiff and lose their ability to function. Having variants of the HLA-DPB1 gene that contain the protein building block (amino acid) glutamic acid at position 69 (written as E69) increases the risk of developing beryllium sensitization or chronic beryllium disease.

     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).

Conditions with Increased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Conditions with Decreased Gene Activity

Condition Change (log2fold) Comparison Species Experimental variables Experiment name

Technical

The following transcription factors affect gene expression:

  • MEF-2A
  • HNF-4alpha1
  • Bach1
  • USF1
  • USF-1

Gene Pathways:

  • Rheumatoid arthritis
  • Viral myocarditis
  • Immune System
  • Antigen processing and presentation
  • Staphylococcus aureus infection
  • Asthma
  • Tuberculosis
  • Toxoplasmosis
  • Systemic lupus erythematosus
  • Leishmaniasis
  • Intestinal immune network for IgA production
  • Allograft rejection
  • Cell adhesion molecules (CAMs)
  • Type I diabetes mellitus
  • Graft-versus-host disease
  • Autoimmune thyroid disease
  • Phagosome

Molecular Function:

  • Peptide Antigen Binding

Biological Processes:

  • Antigen Processing And Presentation Of Exogenous Peptide Antigen Via Mhc Class Ii
  • Interferon-Gamma-Mediated Signaling Pathway
  • Positive Regulation Of Interferon-Gamma Production
  • Positive Regulation Of T Cell Activation
  • Positive Regulation Of T Cell Proliferation
  • T Cell Costimulation
  • T Cell Receptor Signaling Pathway
*synonyms

Synonyms/Aliases/Alternative Names of the Gene:

DPB1| HLA class II histocompatibility antigen, DP beta 1 chain| HLA class II histocompatibility antigen, DP(W4) beta chain| HLA-DP| HLA-DP1B| HLA-DPB| HLA-DP histocompatibility type, beta-1 subunit| MHC class II antigen DPB1| MHC class II HLA-DP-beta-1| MHC HLA DPB1| hla-dpb1

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