HLA-DRB1

Last updated

HLA-DRB1
1AQD.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases HLA-DRB1 , DRB1, DRw10, HLA-DR1B, HLA-DRB, SS1, major histocompatibility complex, class II, DR beta 1
External IDs OMIM: 142857; MGI: 95901; HomoloGene: 136635; GeneCards: HLA-DRB1; OMA:HLA-DRB1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001243965
NM_002124
NM_001359193
NM_001359194

NM_010382

RefSeq (protein)

NP_001230894
NP_002115
NP_001346122
NP_001346123
NP_002115.2

NP_034512

Location (UCSC) Chr 6: 32.58 – 32.59 Mb Chr 17: 34.52 – 34.54 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

HLA class II histocompatibility antigen, DRB1 beta chain is a protein that in humans is encoded by the HLA-DRB1 gene. [5] DRB1 encodes the most prevalent beta subunit of HLA-DR. DRB1 alleles, especially those encoding amino acid sequence changes at positions 11 and 13, are associated risk of rheumatoid arthritis. [6] [7]

Function

The protein encoded by this gene belongs to the HLA class II beta chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DRA) and a beta chain (DRB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins to T helper cells. Class II molecules are constitutively expressed in professional antigen-presenting cells (APC: B lymphocytes, dendritic cells, macrophages), [5] and could be induced in non-professional APCs.

There is evidence it is associated with reduced severity of COVID-19 disease. [8]

Gene structure and polymorphisms

The beta chain is approximately 26-28 kDa. It is encoded by 6 exons, exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. To date, more than 3,700 HLA-DRB1 alleles have been described and made publicaly available in the IPD-IMGT/HLA Database. [9] HLA typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. [5]

Gene expression

DRB1 is expressed at a level five times higher than its paralogues DRB3, DRB4 and DRB5. DRB1 is present in all individuals. Allelic variants of DRB1 are linked with either none or one of the genes DRB3, DRB4 and DRB5. There are 5 related pseudogenes: DRB2, DRB6, DRB7, DRB8 and DRB9. [5]

Prevalence of the HLA-DRB1*10:01 allele was greatly increased in people with anti-IgLON5 disease. [10]

See also

Related Research Articles

<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 is a complex of genes on chromosome 6 in humans that 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">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-DR53</span>

HLA-DR53 is an HLA-DR serotype that recognizes gene products of HLA-DRB4 locus. There are 13 alleles at this locus that encode 7 proteins.

<span class="mw-page-title-main">HLA-DR52</span>

HLA-DR52 is an HLA-DR serotype that recognizes gene products of HLA-DRB3 locus. Three allele groups can produce 35 isoforms.

<span class="mw-page-title-main">HLA-DRB4</span> Protein-coding gene in the species Homo sapiens

Major histocompatibility complex, class II, DR beta 4, also known as HLA-DRB4, is a human gene.

<span class="mw-page-title-main">HLA-DRB5</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DRB5 beta chain is a protein that in humans is encoded by the HLA-DRB5 gene.

<span class="mw-page-title-main">HLA-DR51</span>

HLA-DR51 is a HLA-DR serotype that recognizes the antigens encoded by the minor DR locus HLA-DRB5.

<span class="mw-page-title-main">HLA-DR14</span>

HLA-DR14(DR14) is a HLA-DR serotype that recognizes the DRB1*1401 to *1408, *1410 to *1418, and other *14 gene products. DR14 serotype is a split antigen of the older HLA-DR6 serotype group which also contains the similar HLA-DR13 antigens.

<span class="mw-page-title-main">HLA-DR4</span>

HLA-DR4 (DR4) is an HLA-DR serotype that recognizes the DRB1*04 gene products. The DR4 serogroup is large and has a number of moderate frequency alleles spread over large regions of the world.

<span class="mw-page-title-main">HLA-DR1</span>

HLA-DR1 (DR1) is a HLA-DR serotype that recognizes the DRB1*01 gene products. It has been observed to be common among centenarians.

<span class="mw-page-title-main">HLA-DQB1</span> Protein-coding gene in the species Homo sapiens

Major histocompatibility complex, class II, DQ beta 1, also known as HLA-DQB1, is a human gene and also denotes the genetic locus that contains this gene. The protein encoded by this gene is one of two proteins that are required to form the DQ heterodimer, a cell surface receptor essential to the function of the immune system.

<span class="mw-page-title-main">Major histocompatibility complex, class II, DQ alpha 1</span> Protein-coding gene in the species Homo sapiens

Major histocompatibility complex, class II, DQ alpha 1, also known as HLA-DQA1, is a human gene present on short arm of chromosome 6 (6p21.3) and also denotes the genetic locus which contains this gene. The protein encoded by this gene is one of two proteins that are required to form the DQ heterodimer, a cell surface receptor essential to the function of the immune system.

<span class="mw-page-title-main">HLA-DPB1</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DP(W2) beta chain is a protein that in humans is encoded by the HLA-DPB1 gene.

<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-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">TAP2</span> Protein-coding gene in the species Homo sapiens

TAP2 is a gene in humans that encodes the protein Antigen peptide transporter 2.

Major histocompatibility complex, class II, DP alpha 1, also known as HLA-DPA1, is a human gene.

References

  1. 1 2 3 ENSG00000206240, ENSG00000229074, ENSG00000196126, ENSG00000206306, ENSG00000228080 GRCh38: Ensembl release 89: ENSG00000236884, ENSG00000206240, ENSG00000229074, ENSG00000196126, ENSG00000206306, ENSG00000228080 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000060586 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 3 4 "Entrez Gene: HLA-DRB1 major histocompatibility complex, class II, DR beta 1".
  6. Gregersen PK, Silver J, Winchester RJ (November 1987). "The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis". Arthritis and Rheumatism. 30 (11): 1205–13. doi: 10.1002/art.1780301102 . PMID   2446635.
  7. Raychaudhuri S, Sandor C, Stahl EA, Freudenberg J, Lee HS, Jia X, et al. (January 2012). "Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis". Nature Genetics. 44 (3): 291–296. doi:10.1038/ng.1076. PMC   3288335 . PMID   22286218.
  8. Langton DJ, Bourke SC, Lie BA, Reiff G, Natu S, Darlay R, et al. (July 2021). "The influence of HLA genotype on the severity of COVID-19 infection". HLA. 98 (1): 14–22. doi: 10.1111/tan.14284 . PMC   8251294 . PMID   33896121.
  9. Barker DJ, Maccari G, Georgiou X, Cooper MA, Flicek P, Robinson J, et al. (January 2023). "The IPD-IMGT/HLA Database". Nucleic Acids Research. 51 (D1): D1053–D1060. doi:10.1093/nar/gkac1011. PMC   9825470 . PMID   36350643.
  10. Gaig C, Graus F, Compta Y, Högl B, Bataller L, Brüggemann N, et al. (May 2017). "Clinical manifestations of the anti-IgLON5 disease". Neurology. 88 (18): 1736–1743. doi:10.1212/WNL.0000000000003887. PMC   5409845 . PMID   28381508.

Further reading