HLA-DR3

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DR Illustration.PNG
major histocompatibility complex, class II, DR3
Haplotypes groupsDRA*01:DRB1*03:01 DRA*01:DRB1*03:02 DRA*01:DRB1*03:03 DRA*01:DRB1*03:04
Structure (See HLA-DR)
Identifiers
alpha *01:01
Symbol(s) HLA-DRA [ permanent dead link ‍]
EBI-HLA DRA*01:01
Identifiers
beta 1 *03:01*03:01*03:02*03:03*03:04
Symbol(s) HLA-DRB1 [ permanent dead link ‍]
EBI-HLA DRB1*03:01
EBI-HLA DRB1*03:02
EBI-HLA DRB1*03:03
EBI-HLA DRB1*03:04
EBI-HLA DRB1*03:05 Archived 2007-09-26 at the Wayback Machine
Shared data
Locus chr.6 6p21.31

HLA-DR3 is composed of the HLA-DR17 and HLA-DR18 split 'antigens' serotypes. DR3 is a component gene-allele of the AH8.1 haplotype in Northern and Western Europeans. Genes between B8 and DR3 on this haplotype are frequently associated with autoimmune disease. Type 1 diabetes mellitus is associated with HLA-DR3 or HLA-DR4. Nearly half the US population has either DR3 or DR4 (only 1–3% have both), yet only a small percentage (about 0.5%) of these individuals will develop type 1 diabetes.

Contents

Serology

DR17 and DR3 recognition of some DRB1*03 alleles [1]
DRB1*DR3DR17DR18Sample
allele % % %size (N)
03:01336409698
03:0224366317
03:0340605
03:0460205
03:07>501

Some DR3 also react with HLA-DR17 and/or HLA-DR18. The DRB1*03:04 primarily reacts with DR3. The serotypes of *03:05, *03:06, *03:08 to *03:31 are unknown.

Disease associations

By serotype

HLA-DR3 is associated with early-age onset myasthenia gravis, Hashimoto's thyroiditis (along with DR5), primary sclerosing cholangitis, [2] and opportunistic infections in AIDS, [3] but lowered risk for cancers. [4] It is also associated with membranous glomerulonephritis [5]

By allele

DRB1*03:01 (see HLA-DR17)

DRB1*03:02 (See HLA-DR18)

DRB1*03:04 is associated with Graves disease [6]

By haplotypes

DR3 and/or DQ2 is associated with Moreen's ulceration, [7] "bout onset" multiple sclerosis, [8] Graves' disease [9] and systemic lupus erythematosus [10]

DR3-DQ2 linkage is associated with coeliac disease, dermatitis herpetiformis, Diabetes mellitus type 1. DR3-DQ2 is the serological marker for HLA-DQ2.5cis isoform. Although it cannot identify the alpha ".5" chain of HLA DQ, DQA1*05:01 gene is almost always found within the DR3-DQ2 haplotype Eurasia (however in older studies DQA1*05:05 is commonly confused with DQA1*05:01)
[11]

Genetic linkage

DR3 is genetically linked to HLA-DR52, DRB3*02:02 allele, and HLA-DQ2 (DQ2.5).

Related Research Articles

<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-DQ</span> Cell surface receptor protein found on antigen-presenting cells.

HLA-DQ (DQ) is a cell surface receptor protein found on antigen-presenting cells. It is an αβ heterodimer of type MHC class II. The α and β chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chromosome band 6p21.3. Both α-chain and β-chain vary greatly. A person often produces two α-chain and two β-chain variants and thus 4 isoforms of DQ. The DQ loci are in close genetic linkage to HLA-DR, and less closely linked to HLA-DP, HLA-A, HLA-B and HLA-C.

HLA DR3-DQ2 is a double serotype that specifically recognizes cells from individuals who carry a multigene HLA DR, DQ haplotype. Certain HLA DR and DQ genes have known involvement in autoimmune diseases. DR3-DQ2, a multigene haplotype, stands out in prominence because it is a factor in several prominent diseases, namely coeliac disease and juvenile diabetes. In coeliac disease, the DR3-DQ2 haplotype is associated with highest risk for disease in first degree relatives, highest risk is conferred by DQA1*0501:DQB1*0201 homozygotes and semihomozygotes of DQ2, and represents the overwhelming majority of risk. HLA DR3-DQ2 encodes DQ2.5cis isoform of HLA-DQ, this isoform is described frequently as 'the DQ2 isoform', but in actuality there are two major DQ2 isoform. The DQ2.5 isoform, however, is many times more frequently associated with autoimmune disease, and as a result to contribution of DQ2.2 is often ignored.

<span class="mw-page-title-main">HLA-DQ8</span>

HLA-DQ8 (DQ8) is a human leukocyte antigen serotype within the HLA-DQ (DQ) serotype group. DQ8 is a split antigen of the DQ3 broad antigen. DQ8 is determined by the antibody recognition of β8 and this generally detects the gene product of DQB1*0302.

<span class="mw-page-title-main">HLA-DQ2</span> Human leukocyte antigen serotype

HLA-DQ2 (DQ2) is a serotype group within HLA-DQ (DQ) serotyping system. The serotype is determined by the antibody recognition of β2 subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ2 are encoded by the HLA-DQB1*02 allele group. This group currently contains two common alleles, DQB1*0201 and DQB1*0202. HLA-DQ2 and HLA-DQB1*02 are almost synonymous in meaning. DQ2 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ2.2 and DQ2.5, are also encoded by the DQA1*0201 and DQA1*0501 genes, respectively.

<span class="mw-page-title-main">HLA-DQ4</span>

HLA-DQ4 (DQ4) is a serotype subgroup within HLA-DQ(DQ) serotypes. The serotype is determined by the antibody recognition of β4 subset of DQ β-chains. The β-chain of DQ is encoded by HLA-DQB1 locus and DQ4 are encoded by the HLA-DQB1*04 allele group. This group currently contains 2 common alleles, DQB1*0401 and DQB1*0402. HLA-DQ4 and HLA-DQB1*04 are almost synonymous in meaning. DQ4 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. These isoforms, nicknamed DQ4.3 and DQ4.4, are also encoded by the DQA1*0303 and DQA1*0401 genes, respectively.

<span class="mw-page-title-main">HLA-DQ6</span>

HLA-DQ6 (DQ6) is a human leukocyte antigen serotype within HLA-DQ (DQ) serotype group. The serotype is determined by the antibody recognition of β6 subset of DQ β-chains. The β-chain of DQ isoforms are encoded by HLA-DQB1 locus and DQ6 are encoded by the HLA-DQB1*06 allele group. This group currently contains many common alleles, DQB1*0602 is the most common. HLA-DQ6 and DQB1*06 are almost synonymous in meaning. DQ6 β-chains combine with α-chains, encoded by genetically linked HLA-DQA1 alleles, to form the cis-haplotype isoforms. For DQ6, however, cis-isoform pairing only occurs with DQ1 α-chains. There are many haplotypes of DQ6.

<span class="mw-page-title-main">HLA-DQ9</span>

HLA-DQ9 (DQ9) is a human leukocyte antigen serotype within the HLA-DQ (DQ) serotype group. DQ9 is a split antigen of the DQ3 broad antigen. DQ9 is determined by the antibody recognition of β9 and this generally detects the gene product of DQB1*0303.

<span class="mw-page-title-main">HLA-DQ7</span>

HLA-DQ7 (DQ7) is an HLA-DQ serotype that recognizes the common HLA DQB1*0301 and the less common HLA DQB1*0304 gene products. DQ7 is a form of 'split antigen' of the broad antigen group DQ3 which also contains DQ8 and DQ9.

<span class="mw-page-title-main">HLA-DQ1</span> Serotype that covers a broad range of HLA-DQ haplotypes.

HLA-DQ1 is a serotype that covers a broad range of HLA-DQ haplotypes. Historically it was identified as a DR-like alpha chain called DC1; later, it was among 3 types DQw1, DQw2 and DQw3. Of these three serotyping specificities only DQw1 recognized DQ alpha chain. The serotype is positive in individuals who bear the DQA1*01 alleles. The most frequently found within this group are: DQA1*0101, *0102, *0103, and *0104. In the illustration on the right, DQ1 serotyping antibodies recognizes the DQ α (magenta), where antibodies to DQA1* gene products bind variable regions close to the peptide binding pocket.

<span class="mw-page-title-main">HLA-DR17</span>

HLA-DR17 (DR17) is an HLA-DR serotype that recognizes the DRB1*0301 and *0304 gene products. DR17 is found at high frequency in Western Europe. DR17 is part of the broader antigen group HLA-DR3 and is very similar to the group HLA-DR18.

<span class="mw-page-title-main">HLA-DR16</span>

HLA-DR16(DR16) is a HLA-DR serotype that recognizes the DRB1*1601, *1602 and *1604 gene products. DR16 is found in the Mediterranean at modest frequencies. DR16 is part of the older HLA-DR2 serotype group which also contains the similar HLA-DR15 antigens.

<span class="mw-page-title-main">HLA-DR11</span>

HLA-DR11 (DR11) is a HLA-DR serotype that recognizes the DRB1*1101 to *1110. DR11 serotype is a split antigen of the older HLA-DR5 serotype group which also contains the similar HLA-DR12 antigens.

<span class="mw-page-title-main">HLA-DR12</span>

HLA-DR12(DR12) is a HLA-DR serotype that recognizes the DRB1*1201 to *1203, *1206. DR12 serotype is a split antigen of the older HLA-DR5 serotype group which also contains the similar HLA-DR11 antigens.

<span class="mw-page-title-main">HLA-DR7</span>

HLA-DR7 (DR7) is a HLA-DR serotype that recognizes the DRB1*0701 to *0705 gene products.

<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.

In autoimmune disease, anti-apolipoprotein H (AAHA) antibodies, also called anti-β2 glycoprotein I antibodies, comprise a subset of anti-cardiolipin antibodies and lupus anticoagulant. These antibodies are involved in sclerosis and are strongly associated with thrombotic forms of lupus. As a result, AAHA are strongly implicated in autoimmune deep vein thrombosis.

<span class="mw-page-title-main">HLA-A33</span> Human leukocyte antigen serotype

HLA-A33 (A33) is a human leukocyte antigen serotype within HLA-A serotype group. The serotype is determined by the antibody recognition of α33 subset of HLA-A α-chains. For A33, the alpha "A" chain are encoded by the HLA-A*33 allele group and the β-chain are encoded by B2M locus. A33 and A*33 are almost synonymous in meaning. A33 is a split antigen of the broad antigen serotype A19. A33 is a sister serotype of A29, A30, A31, A32, and A74.

HLA A1-B8-DR3-DQ2 haplotype is a multigene haplotype that covers a majority of the human major histocompatibility complex on chromosome 6. A multigene haplotype is set of inherited alleles covering several genes, or gene-alleles; common multigene haplotypes are generally the result of descent by common ancestry. Chromosomal recombination fragments multigene haplotypes as the distance to that ancestor increases in number of generations.

HLA A1-B8 is a multigene haplotype that covers the MHC Class I region of the human major histocompatibility complex on chromosome 6. A multigene haplotype is set of inherited alleles covering several genes, or gene-alleles; common multigene haplotypes are generally the result of identity by descent from a common ancestor. Chromosomal recombination fragments multigene haplotypes as the distance to that ancestor increases in number of generations.

References

  1. ↑ derived from IMGT/HLA
  2. ↑ Wiencke K, Karlsen TH, Boberg KM, Thorsby E, Schrumpf E, Lie BA, Spurkland A (2007). "Primary sclerosing cholangitis is associated with extended HLA-DR3 and HLA-DR6 haplotypes". Tissue Antigens. 69 (2): 161–9. doi:10.1111/j.1399-0039.2006.00738.x. PMID   17257319.
  3. ↑ Pollack MS, Gold J, Metroka CE, Safai B, Dupont B (1984). "HLA-A,B,C and DR antigen frequencies in acquired immunodeficiency syndrome (AIDS) patients with opportunistic infections". Hum. Immunol. 11 (2): 99–103. doi:10.1016/0198-8859(84)90048-X. PMID   6333416.
  4. ↑ Mann DL, Murray C, O'Donnell M, Blattner WA, Goedert JJ (1990). "HLA antigen frequencies in HIV-1-related Kaposi's sarcoma". J. Acquir. Immune Defic. Syndr. 3 (Suppl 1): S51–5. PMID   2395088.
  5. ↑ Weil L (2014). Quick Reference Guide to Medicine and Surgery. Edinburgh: Mosby: Elsevier. p. 287. ISBN   978-0-7234-3553-2.
  6. ↑ Heward, Jm, Allahabadia, A, Sheppard, Mc, Barnett, Ah, Franklyn, Ja, Gough, Sc (Jul 1999). "Association of the large multifunctional proteasome (LMP2) gene with Graves' disease is a result of linkage disequilibrium with the HLA haplotype DRB1*0304-DQB1*02-DQA1*0501". Clinical Endocrinology. 51 (1): 115–8. doi:10.1046/j.1365-2265.1999.00755.x. ISSN   0300-0664. PMID   10468973. S2CID   6376169.
  7. ↑ Taylor C, Smith S, Morgan C, Stephenson S, Key T, Srinivasan M, Cunningham E, Watson P (2000). "HLA and Mooren's ulceration". Br J Ophthalmol. 84 (1): 72–5. doi:10.1136/bjo.84.1.72. PMC   1723219 . PMID   10611103.
  8. ↑ Weinshenker B, Santrach P, Bissonet A, McDonnell S, Schaid D, Moore S, Rodriguez M (1998). "Major histocompatibility complex class II alleles and the course and outcome of MS: a population-based study". Neurology. 51 (3): 742–7. doi:10.1212/wnl.51.3.742. PMID   9748020. S2CID   11416838.
  9. ↑ Ratanachaiyavong S, Lloyd L, Darke C, McGregor A (1993). "MHC-extended haplotypes in families of patients with Graves' disease". Hum Immunol. 36 (2): 99–111. doi:10.1016/0198-8859(93)90112-E. PMID   8096501.
  10. ↑ Tjernström F, Hellmer G, Nived O, Truedsson L, Sturfelt G (1999). "Synergetic effect between interleukin-1 receptor antagonist allele (IL1RN*2) and MHC class II (DR17,DQ2) in determining susceptibility to systemic lupus erythematosus". Lupus. 8 (2): 103–8. doi:10.1191/096120399678847560. PMID   10192503. S2CID   26486050.
  11. ↑ Pera C, Delfino L, Longo A, Pistillo MP, Ferrara GB (March 2000). "Novel associations among HLA-DQA1 and -DQB1 alleles, revealed by high-resolution sequence-based typing (SBT)". Tissue Antigens. 55 (3): 275–9. doi:10.1034/j.1399-0039.2000.550313.x. PMID   10777105.
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