HLA-B

Last updated
HLA-B
HLA-B.png
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases HLA-B , AS, SPDA1, Bw-47, Bw-50, major histocompatibility complex, class I, B, B-4901, B-5001, HEL-S-83, HLA-B*45ZJ, HLA-B-3506, HLA-B-3905, HLA-B-5502, HLA-B-5602, HLA-B15, HLA-B39, HLA-B49, HLA-B50, HLA-B55, HLA-B59, HLA-B61, HLA-Cw, HLA-DRB1
External IDs HomoloGene: 134029 GeneCards: HLA-B
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005514

n/a

RefSeq (protein)

NP_005505

n/a

Location (UCSC) Chr 6: 31.35 – 31.37 Mb n/a
PubMed search [2] n/a
Wikidata
View/Edit Human

HLA-B (major histocompatibility complex, class I, B) is a human gene that provides instructions for making a protein that plays a critical role in the immune system. HLA-B 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.

HLA is the human version of the major histocompatibility complex (MHC), a gene family that occurs in many species. Genes in this complex are separated into three basic groups: class I, class II, and class III. In humans, the HLA-B gene and two related genes, HLA-A and HLA-C, are the major genes in MHC class I.

MHC class I genes provide instructions for making proteins that are present on the surface of almost all cells. On the cell surface, these proteins are bound to protein fragments (peptides) that have been exported from within the cell. MHC class I proteins display these peptides to the immune system. If the immune system recognizes the peptides as foreign (such as viral or bacterial peptides), it responds by destroying the infected cell.

The HLA-B gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign invaders. Hundreds of versions (alleles) of HLA-B are known, each of which is given a particular number (such as HLA-B27). Closely related alleles are categorized together; for example, at least 28 very similar alleles are subtypes of HLA-B27. These subtypes are designated as HLA-B*2701 to HLA-B*2728.

The HLA-B gene is located on the short (p) arm of chromosome 6 at cytoband 21.3, from base pair 31,353,871 to 31,357,211 [3]

Serotypes of HLA-B gene products
antigen-Broad
antigen
Split antigens
B7 B5 B51 B52
B8 B12 B44 B45
B13 B14 B64 B65
B18 B15 B62 B63 B70
B27 B72 B75 B77
B35 B16 B38 B39
B37 B17 B57 B58
B41 B21 B49 B50
B42 B22 B54 B55 B56
B46 B40 B60 B61
B47
B48
B53
B59
B67
B73
B78
B81
B*82
B*83
"HLA-" prefix trimmed from serotype names.

Ankylosing spondylitis: A version of the HLA-B gene called HLA-B27 increases the risk of developing ankylosing spondylitis. It is uncertain how HLA-B27 causes this increased risk. Researchers speculate that HLA-B27 may abnormally display to the immune system peptides that trigger arthritis. Other research suggests that joint inflammation characteristic of this disorder may result from improper folding of the HLA-B27 protein or the presence of abnormal forms of the protein on the cell surface. Although most patients with ankylosing spondylitis have the HLA-B27 variation, many people with this particular variation never develop the disorder. Other genetic and environmental factors are likely to affect the chances of developing ankylosing spondylitis and influence its progression.

In addition to Ankylosing spondylitis, HLA-B27 is associated with other spondyloarthropathies, a group of related inflammatory joint diseases. Some of these diseases are associated with a common skin condition called psoriasis or chronic inflammatory bowel disorders (Crohn's disease and ulcerative colitis). One of the spondyloarthropathies, reactive arthritis, is typically triggered by bacterial infections of the gastrointestinal or genital tract. Following an infection, affected individuals may develop arthritis, back pain, and eye inflammation. Like ankylosing spondylitis, many factors probably contribute to the development of reactive arthritis and other spondyloarthropathies.

A large number of studies have shown an association between HLA-B51 And Behçet's disease.

Other disorders: Several variations of the HLA-B gene are associated with adverse reactions to certain drugs. For example, two specific versions of this gene are related to increased drug sensitivity among the Han Chinese population. Individuals who have HLA-B*1502 are more likely to experience a severe skin disorder called Stevens–Johnson syndrome in response to carbamazepine (a drug used to treat seizures). Another version, HLA-B*5801, is associated with an increased risk of severe skin reactions in people treated with allopurinol (a drug used to treat gout, which is a form of arthritis caused by uric acid in the joints).

Among people with human immunodeficiency virus (HIV) infection, a version of HLA-B designated HLA-B*5701 is associated with an extreme sensitivity to abacavir. This drug is a treatment for HIV-1 that slows the spread of the virus in the body. People with abacavir hypersensitivity often develop a fever, chills, rash, upset stomach, and other symptoms when treated with this drug.

Several other variations of the HLA-B gene appear to play a role in the progression of HIV infection to acquired immunodeficiency syndrome (AIDS). AIDS is a disease that damages the immune system, preventing it from effectively defending the body against infections. The signs and symptoms of AIDS may not appear until 10 years or more after infection with HIV. Studies suggest that people with HIV infection who have HLA-B27 or HLA-B57 tend to progress more slowly than usual to AIDS. On the other hand, researchers believe that HIV-positive individuals who have HLA-B35 tend to develop the signs and symptoms of AIDS more quickly than usual. Other factors also influence the progression of HIV to AIDS.

Another version of the HLA-B gene, HLA-B53, has been shown to help protect against severe malaria. [4] HLA-B53 is most common in West African populations, where malaria is a frequent cause of death in children. Researchers suggest that this version of the HLA-B gene may help the immune system respond more effectively to the parasite that causes malaria.

HLA-B and graft compatibility

HLA-B is one of three major HLAs that should be matched between donors and recipients. They are HLA-A, HLA-B, (both Class I MHCs) and HLA-DR (a Class II MHC). [5] If the two tissues have the same genes coding for these three HLAs, the likelihood and severity of rejection is minimized. [6]

See also

Related Research Articles

<span class="mw-page-title-main">Autoimmunity</span> Immune response against an organisms own healthy cells

In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". Prominent examples include celiac disease, post-infectious IBS, diabetes mellitus type 1, Henoch–Schönlein purpura (HSP) sarcoidosis, systemic lupus erythematosus (SLE), Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis (RA), ankylosing spondylitis, polymyositis (PM), dermatomyositis (DM), and multiple sclerosis (MS). Autoimmune diseases are very often treated with steroids.

<span class="mw-page-title-main">Major histocompatibility complex</span> Cell surface proteins, part of the acquired immune system

The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules.

<span class="mw-page-title-main">Human leukocyte antigen</span> Genes on human chromosome 6

The human leukocyte antigen (HLA) system or complex is a complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histocompatibility complex (MHC) found in many animals.

<span class="mw-page-title-main">Ankylosing spondylitis</span> Type of arthritis in which there is long-term inflammation of the joints of the spine

Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine, typically where the spine joins the pelvis. Occasionally, areas affected may include other joints such as the shoulders or hips. Eye and bowel problems may occur as well as back pain. Joint mobility in the affected areas generally worsens over time.

<span class="mw-page-title-main">HLA-B27</span> Type of antigen

Human leukocyte antigen (HLA) B27 is a class I surface antigen encoded by the B locus in the major histocompatibility complex (MHC) on chromosome 6 and presents antigenic peptides to T cells. HLA-B27 is strongly associated with ankylosing spondylitis and other associated inflammatory diseases, such as psoriatic arthritis, inflammatory bowel disease, and reactive arthritis.

Spondyloarthropathy or spondyloarthrosis refers to any joint disease of the vertebral column. As such, it is a class or category of diseases rather than a single, specific entity. It differs from spondylopathy, which is a disease of the vertebra itself, but many conditions involve both spondylopathy and spondyloarthropathy.

<span class="mw-page-title-main">Abacavir</span> Chemical compound

Abacavir, sold under the brand name Ziagen among others, is a medication used to treat HIV/AIDS. Similar to other nucleoside analog reverse-transcriptase inhibitors (NRTIs), abacavir is used together with other HIV medications, and is not recommended by itself. It is taken by mouth as a tablet or solution and may be used in children over the age of three months.

<span class="mw-page-title-main">MHC class I</span> Protein of the immune system

MHC class I molecules are one of two primary classes of major histocompatibility complex (MHC) molecules and are found on the cell surface of all nucleated cells in the bodies of vertebrates. They also occur on platelets, but not on red blood cells. Their function is to display peptide fragments of proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen displayed with the help of an MHC class I protein. Because MHC class I molecules present peptides derived from cytosolic proteins, the pathway of MHC class I presentation is often called cytosolic or endogenous pathway.

<span class="mw-page-title-main">HLA-DR</span> Subclass of HLA-D antigens that consist of alpha and beta chains

HLA-DR is an MHC class II cell surface receptor encoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31. The complex of HLA-DR and peptide, generally between 9 and 30 amino acids in length, constitutes a ligand for the T-cell receptor (TCR). HLA were originally defined as cell surface antigens that mediate graft-versus-host disease. Identification of these antigens has led to greater success and longevity in organ transplant.

<span class="mw-page-title-main">HLA-DRA</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DR alpha chain is a protein that in humans is encoded by the HLA-DRA gene. HLA-DRA encodes the alpha subunit of HLA-DR. Unlike the alpha chains of other Human MHC class II molecules, the alpha subunit is practically invariable. However it can pair with, in any individual, the beta chain from 3 different DR beta loci, DRB1, and two of any DRB3, DRB4, or DRB5 alleles. Thus there is the potential that any given individual can form 4 different HLA-DR isoforms.

<span class="mw-page-title-main">HLA-A</span> Protein-coding gene in the species Homo sapiens

HLA-A is a group of human leukocyte antigens (HLA) that are encoded by the HLA-A locus, which is located at human chromosome 6p21.3. HLA is a major histocompatibility complex (MHC) antigen specific to humans. HLA-A is one of three major types of human MHC class I transmembrane proteins. The others are HLA-B and HLA-C. The protein is a heterodimer, and is composed of a heavy α chain and smaller β chain. The α chain is encoded by a variant HLA-A gene, and the β chain (β2-microglobulin) is an invariant β2 microglobulin molecule. The β2 microglobulin protein is encoded by the B2M gene, which is located at chromosome 15q21.1 in humans.

<span class="mw-page-title-main">TAP1</span> Protein-coding gene in the species Homo sapiens

Transporter associated with antigen processing 1 (TAP1) is a protein that in humans is encoded by the TAP1 gene. A member of the ATP-binding cassette transporter family, it is also known as ABCB2.

<span class="mw-page-title-main">HLA-DRB3</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DRB3-1 beta chain is a protein that in humans is encoded by the HLA-DRB3 gene.

<span class="mw-page-title-main">HLA-F</span> Protein-coding gene in the species Homo sapiens

HLA class I histocompatibility antigen, alpha chain F is a protein that in humans is encoded by the HLA-F gene. It is an empty intracellular molecule that encodes a non-classical heavy chain anchored to the membrane and forming a heterodimer with a β-2 microglobulin light chain. It belongs to the HLA class I heavy chain paralogues that separate from most of the HLA heavy chains. HLA-F is localized in the endoplasmic reticulum and Golgi apparatus, and is also unique in the sense that it exhibits few polymorphisms in the human population relative to the other HLA genes; however, there have been found different isoforms from numerous transcript variants found for the HLA-F gene. Its pathways include IFN-gamma signaling and CDK-mediated phosphorylation and removal of the Saccharomycescerevisiae Cdc6 protein, which is crucial for functional DNA replication.

<span class="mw-page-title-main">HLA-DMB</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DM beta chain is a protein that in humans is encoded by the HLA-DMB gene.

<span class="mw-page-title-main">HLA-DMA</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DM alpha chain is a protein that in humans is encoded by the HLA-DMA gene.

<span class="mw-page-title-main">ERAP1</span> Protein-coding gene in the species Homo sapiens

Type 1 tumor necrosis factor receptor shedding aminopeptidase regulator, also known as endoplasmic reticulum aminopeptidase 1 (ARTS-1), is a protein which in humans is encoded by the ARTS-1 gene.

<span class="mw-page-title-main">HLA-DOA</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DO alpha chain is a protein that in humans is encoded by the HLA-DOA gene.

<span class="mw-page-title-main">HLA-DOB</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DO beta chain is a protein that in humans is encoded by the HLA-DOB gene.

<span class="mw-page-title-main">HLA-DQB2</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DX beta chain is a protein that in humans is encoded by the HLA-DQB2 gene.

References

  1. 1 2 3 ENSG00000234745, ENSG00000206450, ENSG00000224608, ENSG00000223532, ENSG00000232126 GRCh38: Ensembl release 89: ENSG00000228964, ENSG00000234745, ENSG00000206450, ENSG00000224608, ENSG00000223532, ENSG00000232126 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. "HLA-B gene".
  4. Hill AV, Allsopp CE, Kwiatkowski D, Anstey NM, Twumasi P, Rowe PA, Bennett S, Brewster D, McMichael AJ, Greenwood BM (August 1991). "Common west African HLA antigens are associated with protection from severe malaria". Nature. 352 (6336): 595–600. Bibcode:1991Natur.352..595H. doi: 10.1038/352595a0 . PMID   1865923. S2CID   2667496.
  5. Fix M (1998). "HLA Matching, Antibodies, and You". Kidney Transplantation: Past, Present, and Future. University of Michigan Medical Center/Stanford University. Retrieved 14 Dec 2013.
  6. Solomon S, Pitossi F, Rao MS (February 2015). "Banking on iPSC--is it doable and is it worthwhile". Stem Cell Reviews. 11 (1): 1–10. doi:10.1007/s12015-014-9574-4. PMC   4333229 . PMID   25516409.

Further reading

This article incorporates public domain text from The U.S. National Library of Medicine