View source for HLA-DR

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| update_page = yes 
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{{GNF_Protein_box
 | image = PBB_Protein_HLA-DRA_image.jpg
 | image_source = [[Protein_Data_Bank|PDB]] rendering based on 1a6a.
 | Name = Major histocompatibility complex, class II, DR alpha
 | HGNCid = 4947
 | Symbol = HLA-DRA
 | AltSymbols =; HLA-DRA1
 | OMIM = 142860
 | ECnumber =  
 | Homologene = 7751
 | MGIid = 95900
 | GeneAtlas_image1 = PBB_GE_HLA-DRA_208894_at_tn.png
 | GeneAtlas_image2 = PBB_GE_HLA-DRA_210982_s_at_tn.png
 | Function = {{GNF_GO|id=GO:0032395 |text = MHC class II receptor activity}} 
 | Component = {{GNF_GO|id=GO:0005764 |text = lysosome}} {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0042613 |text = MHC class II protein complex}} 
 | Process = {{GNF_GO|id=GO:0002504 |text = antigen processing and presentation of peptide or polysaccharide antigen via MHC class II}} {{GNF_GO|id=GO:0006955 |text = immune response}} 
 | Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 3122
    | Hs_Ensembl = ENSG00000204287
    | Hs_RefseqProtein = NP_061984
    | Hs_RefseqmRNA = NM_019111
    | Hs_GenLoc_db =  
    | Hs_GenLoc_chr = 6
    | Hs_GenLoc_start = 32515597
    | Hs_GenLoc_end = 32520943
    | Hs_Uniprot =  
    | Mm_EntrezGene = 14968
    | Mm_Ensembl = ENSMUSG00000036322
    | Mm_RefseqmRNA = NM_010381
    | Mm_RefseqProtein = NP_034511
    | Mm_GenLoc_db =  
    | Mm_GenLoc_chr = 17
    | Mm_GenLoc_start = 33950514
    | Mm_GenLoc_end = 33952226
    | Mm_Uniprot = O19462
  }}
}}


==Overview==
'''HLA-DR''' is a [[major histocompatibility complex]], [[MHC class II]], [[cell surface receptor]]
encoded by the [[human leukocyte antigen]] complex on chromosome 6 region 6p21.31.
Receptor is frequently found with [[ligand]], a peptide of 9 amino acids in length or longer, within the binding groove. The receptor/peptide complex is a ligand for
T-cell receptor (TCR). HLA, [[human leukocyte antigens]], were originally defined
as cell surface antigens that mediate [[graft-versus-host disease]], which resulted in the
rejection of tissue transplants in HLA mismatched donors. Identification of these
antigens has led to greater success and longevity in organ transplant. 

HLA-DR is also involved in several autoimmune conditions, disease susceptibility
and disease resistance. It is also closely linked to [[HLA-DQ]] and this linkage often makes it difficult to resolve the more causative factor in disease.  

HLA-DR molecules are upregulated in response to signalling. In the instance
of an infection, the peptide (such as the staphlococcal enterotoxin I peptide show in the two illustrations) is bound into a DR molecule and presented to a few of a great many T-cell
receptors found on T-helper cells. These cells then bind to antigens on the surface
of B-cells stimulating B-cell proliferation. 

==Function==
[[Image:DR_Pept_TCR.JPG|frame|left|Illustration of DR receptor presenting antigen
to TCR on T-helper cell]]
The primary function of HLA-DR is to present peptide antigens, potentially foreign
in origin, to the immune system for the purpose of eliciting or suppressing T-(helper)-cell responses that eventually lead to the production of antibodies against the same peptide antigen. [[Antigen presenting cells]] (macrophages, B-cells and dendritic cells) are the cells in which DR are typically found. Increased abundance of DR 'antigen' on the cell surface is often in response to stimulation, and, therefore, DR is also a marker for immune stimulation.

==Structure==
HLA-DR is a αβ [[heterodimer]], [[cell surface receptor]], each subunit contains 2 extracellular domains, a membrane spanning domain and a cytoplasmic tail. Both α and β chains are anchored in the membrane. The N-terminal domain of the mature protein forms an alpha-helix that constitutes the exposed part of the binding groove, the C-terminal cytoplasmic region interact with the other chain forming a beta-sheet under the binding groove spanning to the cell membrane. The majority of the peptide contact positions are in the 1st 80 residues of each chain.

==Genetics==

The genetics of HLA-DR is complex because HLA-DR is encoded by several loci and several 'genes' of different function at each locus. 

The '''DR α-chain''' is encoded by the {{Gene|HLA-DRA}} (DRA1) [[locus]]. Unlike the other DR loci functional variation in mature DRA gene products is absent. (Note: see table ''Number of Variant Alleles HLA-DR Loci''- reduces the potential functional combinations from ~1400 to ~400 (table is not exact because new alleles are continually being added not all new alleles are functional variants of the mature subunits)). 

{| border="0" cellspacing="0" cellpadding="0" align="right" style="text-align:center; background:#ffffff; margin-left:2em; border:2px #e0e0ff solid;"
|+ 28 (of 75) Most common DR-DQ haplotypes in Caucasian Americans
|- style = "background:#f0f0ff"
! style = "background:#e8e8f8" |<font color="purple">DR</font>
! <font color="#013220">DR</font>-<font color="purple">DQ</font>
! style = "background:#e7f7f7" | <font color="#013220">DR</font> 
! colspan = "2" style = "background:#f7e7ff" |<font color="purple">DQ</font> 
! colspan = "2" | Freq 
| width = "10" | 
|- style = "background:#f0f0ff"
! style = "background:#e8e8f8; font-size:80%" | Serotype 
| width = "80" | haplotype 
! width = "45" style = "background:#e7f7f7" | <font color="green">B1</font> 
! width = "45" style = "background:#f7e7ff" | <font color="#bb00bb">A1</font> 
! width = "45" style = "background:#f7e7ff" | <font color="blue">B1</font> 
| colspan = "2" | '''%'''<ref name="AmericanCaucDloci">{{cite journal | author = Klitz W, Maiers M, Spellman S, Baxter-Lowe LA, Schmeckpeper B, Williams TM, and Fernandez-Vina M | title = New HLA haplotype frequency reference standards: high-resolution and large sample typing of HLA DR-DQ haplotypes in a sample of European Americans. | journal = Tissue Antigens | volume = 62 | issue = 4 | pages = 296-307 | year = 2003 | id = PMID 12974796}}</ref> 
| 
|- style = "background:#ffffdf"
! style = "background:#f7f7d7" rowspan = "3"  | DR1 
| rowspan = "3" | <font color="#013220">DR1</font>-<font color="purple">DQ5</font> 
| <font color="#013220">0101</font> || <font color="#bb00bb">0101</font> || <font color="blue">0501</font> 
| style = "background:#fbfbfb" align = right  width = "30"| '''9.'''
| style = "background:#fbfbfb" align = left width = "15" | '''1''' 
|- style = "background:#ffffdf"
| <font color="#013220">0102</font> || <font color="#bb00bb">0101</font> || <font color="blue">0501</font> 
| style = "background:#fbfbfb" align = right  width = "30"| '''1.'''
| style = "background:#fbfbfb" align = left width = "15" | '''4''' 
|- style = "background:#ffffdf"
| <font color="#013220">0103</font> || <font color="#bb00bb">0101</font> || <font color="blue">0501</font> 
| style = "background:#fbfbfb" align = right  width = "30"| '''0.'''
| style = "background:#fbfbfb" align = left width = "15" | '''5''' 
|- style = "background:#efffdf"
! style = "background:#e7f8d7" | DR3  
| <font color="#013220">DR3</font>-<font color="purple">DQ2</font> || <font color="#013220">0301</font> || <font color="#bb00bb">0501</font> || <font color="blue">0201</font> 
| style = "background:#fbfbfb" align = right | '''13.'''
| style = "background:#fbfbfb" align = left | '''1''' 
|-  style = "background:#eff7ef"
! style = "background:#e8efe8" rowspan = "7" | DR4 
| rowspan = "2" | <font color="#013220">DR4</font>-<font color="purple">DQ7</font> 
| <font color="#013220">0401</font> || <font color="#bb00bb">0300</font> || <font color="blue">0301</font> 
| style = "background:#fbfbfb" align = right | '''5.'''
| style = "background:#fbfbfb" align = left | '''4''' 
|- style = "background:#eff7ef"
| <font color="#013220">0407</font> || <font color="#bb00bb">0300</font> || <font color="blue">0301</font> 
| style = "background:#fbfbfb" align = right | '''0.'''
| style = "background:#fbfbfb" align = left | '''9''' 
|- style = "background:#eff7ef"
| rowspan = "5" |<font color="#013220">DR4</font>-<font color="purple">DQ8</font> 
| <font color="#013220">0401</font> || <font color="#bb00bb">0300</font> || <font color="blue">0302</font> 
| style = "background:#fbfbfb" align = right | '''5.'''
| style = "background:#fbfbfb" align = left | '''0''' 
|- style = "background:#eff7ef"
| <font color="#013220">0402</font> || <font color="#bb00bb">0300</font> || <font color="blue">0302</font> 
| style = "background:#fbfbfb" align = right | '''1.'''
| style = "background:#fbfbfb" align = left | '''0''' 
|- style = "background:#eff7ef"
| <font color="#013220">0403</font> || <font color="#bb00bb">0300</font> || <font color="blue">0302</font> 
| style = "background:#fbfbfb" align = right | '''0.'''
| style = "background:#fbfbfb" align = left | '''4''' 
|- style = "background:#eff7ef"
| <font color="#013220">0404</font> || <font color="#bb00bb">0300</font> || <font color="blue">0302</font> 
| style = "background:#fbfbfb" align = right | '''3.'''
| style = "background:#fbfbfb" align = left | '''9''' 
|- style = "background:#eff7ef"
| <font color="#013220">0405</font> || <font color="#bb00bb">0300</font> || <font color="blue">0302</font> 
| style = "background:#fbfbfb" align = right | '''0.'''
| style = "background:#fbfbfb" align = left | '''3''' 
|- style = "background:#efefff"
!  style = "background:#e8e8f8" rowspan = "2"  | DR7 
| <font color="#013220">DR7</font>-<font color="purple">DQ2</font> 
| <font color="#013220">0701</font> || <font color="#bb00bb">0201</font> || <font color="blue">0202</font> 
| style = "background:#fbfbfb" align = right | '''11.'''
| style = "background:#fbfbfb" align = left | '''1''' 
|- style = "background:#eeefff"
| <font color="#013220">DR7</font>-<font color="purple">DQ9</font> 
| <font color="#013220">0701</font> || <font color="#bb00bb">0201</font> || <font color="blue">0303</font> 
| style = "background:#fbfbfb" align = right | '''3.'''
| style = "background:#fbfbfb" align = left | '''7''' 
|- style = "background:#f7e7ff"
! style = "background:#efdff7" rowspan = "2" | DR8
| <font color="#013220">DR8</font>-<font color="purple">DQ4</font> 
| <font color="#013220">0801</font> || <font color="#bb00bb">0401</font> || <font color="blue">0402</font> 
| style = "background:#fbfbfb" align = right | '''2.'''
| style = "background:#fbfbfb" align = left | '''2''' 
|- style = "background:#f7e7ff"
| <font color="#013220">DR8</font>-<font color="purple">DQ7</font> 
| <font color="#013220">0803</font> || <font color="#bb00bb">0601</font> || <font color="blue">0301</font> 
| style = "background:#fbfbfb" align = right | '''0.'''
| style = "background:#fbfbfb" align = left | '''1''' 
|- style = "background:#ffe7e7"
! style = "background:#f7dfdf" | DR9
| <font color="#013220">DR9</font>-<font color="purple">DQ9</font> 
| <font color="#013220">0901</font> || <font color="#bb00bb">0300</font> || <font color="blue">0303</font> 
| style = "background:#fbfbfb" align = right | '''0.'''
| style = "background:#fbfbfb" align = left | '''8''' 
|- style = "background:#fff2db"  
! style = "background:#f7e7cf" | DR10 
|<font color="#013220">DR10</font>-<font color="purple">DQ5</font> || <font color="#013220">1001</font> || <font color="#bb00bb">0104</font> || <font color="blue">0501</font>
| style = "background:#fbfbfb" align = right | '''0.'''
| style = "background:#fbfbfb" align = left | '''7''' 
|- style = "background:#ffffdf"
! style = "background:#f7f7d7" rowspan = "3"  | DR11 
| rowspan = "3" | <font color="#013220">DR11</font>-<font color="purple">DQ7</font> 
| <font color="#013220">1101</font> || <font color="#bb00bb">0505</font> || <font color="blue">0301</font> 
| style = "background:#fbfbfb" align = right  width = "30"| '''5.'''
| style = "background:#fbfbfb" align = left width = "15" | '''6''' 
|- style = "background:#ffffdf"
| <font color="#013220">1103</font> || <font color="#bb00bb">0505</font> || <font color="blue">0301</font> 
| style = "background:#fbfbfb" align = right  width = "30"| '''0.'''
| style = "background:#fbfbfb" align = left width = "15" | '''3''' 
|- style = "background:#ffffdf"
| <font color="#013220">1104</font> || <font color="#bb00bb">0505</font> || <font color="blue">0301</font> 
| style = "background:#fbfbfb" align = right  width = "30"| '''2.'''
| style = "background:#fbfbfb" align = left width = "15" | '''7''' 
|- style = "background:#efffdf"
! style = "background:#e7f8d7" | DR12  
| <font color="#013220">DR12</font>-<font color="purple">DQ7</font> || <font color="#013220">1201</font> || <font color="#bb00bb">0505</font> || <font color="blue">0301</font> 
| style = "background:#fbfbfb" align = right | '''1.'''
| style = "background:#fbfbfb" align = left | '''1''' 
|-  style = "background:#eff7ef"
! style = "background:#e8efe8" rowspan = "4" | DR13 
| rowspan = "3" | <font color="#013220">DR13</font>-<font color="purple">DQ6</font> 
| <font color="#013220">1301</font> || <font color="#bb00bb">0103</font> || <font color="blue">0603</font> 
| style = "background:#fbfbfb" align = right | '''5.'''
| style = "background:#fbfbfb" align = left | '''6''' 
|- style = "background:#eff7ef"
| <font color="#013220">1302</font> || <font color="#bb00bb">0102</font> || <font color="blue">0604</font> 
| style = "background:#fbfbfb" align = right | '''3.'''
| style = "background:#fbfbfb" align = left | '''4''' 
|- style = "background:#eff7ef"
| <font color="#013220">1302</font> || <font color="#bb00bb">0102</font> || <font color="blue">0609</font> 
| style = "background:#fbfbfb" align = right | '''0.'''
| style = "background:#fbfbfb" align = left | '''7''' 
|- style = "background:#eff7ef"
|<font color="#013220">DR13</font>-<font color="purple">DQ7</font> 
| <font color="#013220">1303</font> || <font color="#bb00bb">0505</font> || <font color="blue">0301</font> 
| style = "background:#fbfbfb" align = right | '''0.'''
| style = "background:#fbfbfb" align = left | '''7''' 
|- style = "background:#efefff"
!  style = "background:#e8e8f8" | DR14 
| <font color="#013220">DR14</font>-<font color="purple">DQ5</font> 
| <font color="#013220">1401</font> || <font color="#bb00bb">0104</font> || <font color="blue">0503</font> 
| style = "background:#fbfbfb" align = right | '''2.'''
| style = "background:#fbfbfb" align = left | '''0''' 
|- style = "background:#f7e7ff"
! style = "background:#efdff7" rowspan = "2" | DR15
| rowspan = "2" | <font color="#013220">DR15</font>-<font color="purple">DQ6</font> 
| <font color="#013220">1501</font> || <font color="#bb00bb">0102</font> || <font color="blue">0602</font> 
| style = "background:#fbfbfb" align = right | '''14.'''
| style = "background:#fbfbfb" align = left | '''2''' 
|- style = "background:#f7e7ff"
| <font color="#013220">1502</font> || <font color="#bb00bb">0103</font> || <font color="blue">0602</font> 
| style = "background:#fbfbfb" align = right | '''0.'''
| style = "background:#fbfbfb" align = left | '''7''' 
|- style = "background:#ffe7e7"
! style = "background:#f7dfdf" | DR16
| <font color="#013220">DR16</font>-<font color="purple">DQ5</font> 
| <font color="#013220">1601</font> || <font color="#bb00bb">0102</font> || <font color="blue">0502</font> 
| style = "background:#fbfbfb" align = right | '''1.'''
| style = "background:#fbfbfb" align = left | '''0''' 
|- style = "background:#fff7e7"  
|}

The '''DR β-chain'''<ref name = "Marsh"/> is encoded by 4 loci, however no more
than 3 functional loci are present in a single individual, and no more than two on a single chromosome. Sometimes an individual may only possess 2 copies of the same locus,
DRB1*.  The [[HLA-DRB1]] locus is ubiquitous and encodes a very large number of functionally variable gene products ([[HLA-DR1]] to [[HLA-DR17]]). The {{Gene|HLA-DRB3}} locus encodes the [[HLA-DR52]] specificity, is moderately variable and is variably associated with certain [[HLA-DRB1]] types. The {{Gene|HLA-DRB4}} locus encodes the [[HLA-DR53]] specificity, has some variation, and is associated with certain [[HLA-DRB1]] types. The {{Gene|HLA-DRB5}} locus encodes the [[HLA-DR51]] specificity, which is typically invariable, and is linked to the [[HLA-DR2]] types. 

*linkage (See Table)
**[[HLA-DQ|DQA1 and DQB1]] 
***Linkage disequilibrium exists for many [[HLA DR3-DQ2|DR-DQ]] types. 
**Nomenclature issues. Some older studies may refer to DR15 or 16 as DR2 and DQ5 and DQ6 as DQ1 therefore a haplotype DR2-DQ1 is usually referring to DR15-DQ6 but could be referring to DR16-DQ5. DR5 is used to refer to DR11 and DR12, in which case DQ3 might be used. In these instances DQ3 almost always can be interpreted as DQ7, but DR5 is most often DR11 and less frequently DR12. Similar issues exist for DR6 versus DR13 and DR14. DR6-DQ1 can refer to either DR13-DQ6 or less frequently DR14-DQ5, but DR6-DQ3 or DR6-DQ7 generally refers to DR13-DQ7. Even older literature has more confusing designations. By looking at the change of disease association with improved testing we can see how science has evolved over time. 

===Evolution and Allele Frequencies===
There is a high level of allelic diversity at HLA DRB1, it is second only to HLA-B locus in number of allelic variants. These two loci are highest sequence variation rate within human genome. This means [[HLA-DRB1]] is rapidly evolving, much more rapidly than almost all other protein encoding loci. Much of the variation at HLA DRB1 occurs at peptide contact positions in the binding groove, as a result many of the alleles alter the way the DR binds peptide ligands and changes the repertoire each receptor can bind. 
[[Image:DR beta 1 SEI topdown.JPG|left|width|240px|ligand (Staphylococcal enterotoxin 1-C peptide:pkyvkqntlklat) within the binding pocket of DR αβ<sup>101</sup>]] This means that most of the changes are functional in nature, and therefore are under selection. In the HLA region, genes are under heterozygous or balancing selection, although certain alleles appear to be under positive or negative selection, either in the past or present<br />


HLA generally evolve through a process of [[gene conversion]], which is a form of short distance or 'abortive' [[genetic recombination]]. Functional motifs in genes are exchanged to form new alleles, and frequently new, functionally different DR [[isoform]]s. HLA-DR represents an extreme example of this. A survey of X-linked loci reveals that most human loci have undergone fixation within the last 600,000 years, and diploid loci have undergone significant proportion of fixation in that period of time. 

{| border="0" cellspacing="0" cellpadding="0" align="right" style="text-align:center; margin-right: 1em;  border:1px #bbbbff solid; background:#f8f8ff;"
|+ align="left" style = "font-size:90%" |  Number of Variant Alleles HLA-DR Loci 
|- style = "background:#fafaff; font-size:130%" 
! style = "height:30px" colspan="5" align="center" valign = "center" | HLA-DR
|- style = "background:#eeeeff;font-size:100%" 
!  width = "120" | HLA 
|  width = "60" | -'''A1''' 
|  width = "60" | -'''B1''' 
|  width = "85" style = "font-size:90%" | '''-B3 to -B5'''<sup>1</sup> 
|  width = "60" style = "font-size:80%" | Potential 
|- style = "background:#eeeeff;font-size:100%" 
! Locus  
| '''#''' || '''#''' ||'''#'''
|  width = "60" style = "font-size:80%" | Combinations
|- style = "background:#f8f8ff" 
|  style="background:#f4f4ff" | Alleles<ref name=Marsh>{{cite journal | author = Marsh SG, Albert ED, Bodmer WF, Bontrop RE, Dupont B, Erlich HA, Geraghty DE, Hansen JA, Hurley CK, Mach B, Mayr WR, Parham P, Petersdorf EW, Sasazuki T, Schreuder GM, Strominger JL, Svejgaard A, Terasaki PI, and Trowsdale J.  | title = Nomenclature for factors of the HLA System, 2004. | journal = Tissue antigens | volume = 65 | pages = 301-369 | year = 2005 | id = PMID 15787720}}</ref><ref name = "IMGT_HLA">{{cite journal | author = Robinson J, Waller M, Parham P, de Groot N, Bontrop R, Kennedy L, Stoehr P, Marsh S | title = IMGT/HLA and IMGT/MHC: sequence databases for the study of the major histocompatibility complex. | journal = Nucleic Acids Res | volume = 31 | issue = 1 | pages = 311-4 | year = 2003 | id = PMID 12520010}}</ref> 
|  3 || 463  || 74
|  style="background:#fefeff" | 1635
|- style = "background:#f8f8ff" 
|  style="background:#f4f4ff" | Unique Polypeptide
| 2 || 394  ||  57 || style="background:#fefeff" | 902
|- style = "background:#f8f8ff" 
|  style="background:#f4f4ff" | Contact Variant
| 1 || ~300  || ~30 || style="background:#fefeff" |~330
|-
|  colspan="5" style = "font-size:80%" | <sup>1</sup>DRB3, DRB4, DRB5 have variable presence in humans
|}

The level of deep branching at X-linked loci indicates loci were close to fixation or fixed at the end of the human population bottleneck 100,000 to 150,000 years ago. The HLA-DR locus represents a major exception to this observation<ref>{{cite journal | author = Ayala F | title = The myth of Eve: molecular biology and human origins. | journal = Science | volume = 270 | issue = 5244 | pages = 1930-6 | year = 1995 | id = PMID 8533083}}</ref>. Based on distribution of major groupings in the human population it is possible to assert that more than a dozen major variants survived the population bottleneck. This observation is supported by the concept of a heterozygous selection coefficient operating on the HLA-DR, and at the [[HLA-DRB1]] locus to a greater degree relative to {{Gene|HLA-DQB1}} and {{Gene|HLA-DPB1}}. Most of the HLA alleles currently present in the human population can be explained by gene conversion between these ancient ancestral types<ref>{{cite journal | author = Parham P, Ohta T | title = Population biology of antigen presentation by MHC class I molecules. | journal = Science | volume = 272 | issue = 5258 | pages = 67-74 | year = 1996 | id = PMID 8600539}}</ref>, some that persist into the extant population.

=Serogroups=
{| class="wikitable" align="right"
 |+ Subpages for DR serotypes  
 |- 
 | colspan = "3" | Serotypes of [[HLA-DRB1]] gene products
 |- 
 | ''' ''' || colspan = "2" align="center" | Split antigens
 |- 
 | [[HLA-DR1]] || || 
 |- 
 | [[HLA-DR2]] || [[HLA-DR15]] || [[HLA-DR16]] 
 |- 
 | [[HLA-DR3]] || [[HLA-DR17]] || [[HLA-DR18]] 
 |- 
 | [[HLA-DR4]] || || 
 |- 
 | [[HLA-DR5]] || [[HLA-DR11]] || [[HLA-DR12]] 
 |- 
 | [[HLA-DR6]] || [[HLA-DR13]] || [[HLA-DR14]] 
 |- 
 | [[HLA-DR7]] || || 
 |- 
 | [[HLA-DR8]] || || 
 |- 
 | [[HLA-DR9]] || || 
 |- 
 | [[HLA-DR10]] || || 
 |- 
|}

The table provide below links to subpages with information about distribution, genetic
linkage and disease association for the HLA-DR serogroups.


==Interlocus DRB Linkage==
{| class="wikitable"  align="center"
 |+ Subpages for DRB3, -B4, and -B5 serotypes  
 |- 
 | Locus  || Serotype 
 |- 
 | {{Gene|HLA-DRB3}} || [[HLA-DR52]]
 |- 
 | {{Gene|HLA-DRB4}} || [[HLA-DR53]]   
 |- 
 | {{Gene|HLA-DRB5}} || [[HLA-DR51]]  
 |- 
|}

DRB1 is linked with other DRB loci in 4 ways

{| class="wikitable"  align="center"
 |+ DR1 to D17 genetic linkage to DR51, DR52, and DR53  
 |-
 ! width = "70px" | non-DRB1  || colspan = "4" | linked DRB1 antigens
 |- 
 ! antigens  || colspan = "4" |  antigens
 |-
 !  None  
 | align = "center" | DR1 || align = "center" | DR8 || align = "center" | DR10 ||
 |- 
 ! DR51  
 | align = "center" | DR2 || DR15 || DR16 ||  
 |- 
 ! rowspan = "3"  | DR52  
 | align = "center" | DR3 || align = "center" | DR17 || align = "center" | DR18 ||
 |-
 | DR5 || DR11 || DR12 ||
 |-
 | DR6 || DR13 || DR14 ||
 |-
 ! DR53 
 | align = "center" | DR4 || align = "center" | DR7 || align = "center" | DR8 || align = "center" | DR9
 |-
|}

=Associated diseases=
{| class="wikitable"  
 |+ Diseases associated with HLA-DR and links to DR subpages<sup>*</sup>
 |- 
 | colspan = "2" align="center" | Disease  || colspan ="4" align="center" | Associated DR  
 |- 
 | colspan = "2" | [[alopecia areata]]|| [[HLA-DR5|DR5]] || || ||  
 |- 
 | [[anemia]] || [[pernicious anaemia|pernicious]] || [[HLA-DR15|DR15]] || || ||  
 |- 
 | colspan = "2" | [[antiphospholipid syndrome]], primary || [[HLA-DR5|DR5]] || [[HLA-DR12|DR12]]  || ||
 |- 
 | [[aneurysm]] || [[coronary artery]] || [[HLA-DR16|DR16]] || || || 
 |-
 | [[arteritis]] || Takayasu's || [[HLA-DR16|DR16]] || || ||  
 |- 
 | rowspan = "8" | [[arthritis]], [[rheumatoid arthritis|rheumatoid]] || juvenile || [[HLA-DR4|DR4]]  || [[HLA-DR5|DR5]] || [[HLA-DR14|DR14]] || [[HLA-DR15|DR15]]
 |- 
 | pauciarticular, juv. || [[HLA-DR8|DR8]] || || || 
 |- 
 | [[Still's disease]] || [[HLA-DR12|DR12]] || || || 
 |- 
 | [[iritis]] w/juv. arthritis || [[HLA-DR12|DR12]] || || || 
 |- 
 | seronegative || [[HLA-DR1|DR1]] || [[HLA-DR4|DR4]] || || 
 |-
 | w/[[systemic sclerosis]]  || [[HLA-DR1|DR1]] || || ||  
 |-
 | lyme disease induced || [[HLA-DR4|DR4]]  || || ||
 |-
 | tiopronin intolerance || [[HLA-DR5|DR5]]  || [[HLA-DR11|DR11]] || [[HLA-DR12|DR12]] ||
 |- 
 | rowspan = "2" | [[cardiomyopathy]] || hypertrophic || [[HLA-DR4|DR4]] || [[HLA-DR17|DR17]] || ||  
 |- 
 | ''T. cruzi''  induced || [[HLA-DR4|DR4]]  || [[HLA-DR7|DR7]] || [[HLA-DR15|DR15]] ||   
 |- 
 | rowspan = "2" | [[colitis]] || [[Crohn's disease|Crohn's]] || [[HLA-DR1|DR1]] || || ||  
 |- 
 | [[ulcerative colitis|ulcerative]] || [[HLA-DR1|DR1]] || || ||  
 |- 
 | rowspan = "2" | [[diabetes]] || juvenile (type 1) || [[HLA-DR3|DR3]] || [[HLA-DR4|DR4]] || [[HLA-DR17|DR17]] || [[HLA-DR18|DR18]]  
 |- 
 | fatty liver (type 2) || [[HLA-DR8|DR8]] || || ||
 |- 
 | [[encephalomyelitis]]|| rabies vaccine-induced || [[HLA-DR17|DR17]] || || || 
 |- 
 |[[encephalopathy]] || acute necrotizing || [[HLA-DR52|DR52]] || || || 
 |-
 | rowspan = "2" | [[epilepsy]] || childhood || [[HLA-DR5|DR5]] || || ||
 |-
 | infantile/spasm || [[HLA-DR17|DR17]] || || ||  
 |- 
 | [[heart disease]] || rheumatic || [[HLA-DR16|DR16]] || || ||  
 |- 
 | rowspan = "3" | [[hepatitis]] || autoimmune || [[HLA-DR2|DR2]] || [[HLA-DR4|DR4]]  || [[HLA-DR17|DR17]]|| 
 |- 
 | [[primary biliary cirrhosis]] || [[HLA-DR2|DR2]] || [[HLA-DR8|DR8]]  || || 
 |- 
 | chronic type C || [[HLA-DR11|DR11]] || || || 
 |- 
 | colspan = "2" | lichen planus|| [[HLA-DR1|DR1]] || [[HLA-DR10|DR10]] || ||  
 |- 
 | rowspan = "3" | [[lupus]], || systemic  || [[HLA-DR3|DR3]] || [[HLA-DR4|DR4]] || [[HLA-DR52|DR52]]|| 
 |- 
 | hydralazine-induced || [[HLA-DR4|DR4]]|| || ||
 |- 
 | with [[Sjögren's syndrome]] || [[HLA-DR15|DR15]]|| || ||
 |- 
 | [[lymphadenopathy]] || generalized || [[HLA-DR5|DR5]] || || || 
 |- 
 | [[lymphoma]], || [[mycosis fungoides]] || [[HLA-DR5|DR5]] || || ||
 |-
 |colspan = "2" | [[melioidosis]] || [[HLA-DR16|DR16]] || || || 
 |- 
 | rowspan = "2" | [[myasthenia]] || [[myasthenia gravis|gravis]] || [[HLA-DR3|DR3]] || [[HLA-DR6|DR6]] || [[HLA-DR13|DR13]] || [[HLA-DR14|DR14]] 
 |- 
 | penicillamine-induced || [[HLA-DR1|DR1]]  || || || 
 |- 
 | [[myositis]] || inflamatory inclusion body || [[HLA-DR17|DR17]]  || [[HLA-DR18|DR18]] || [[HLA-DR52|DR52]] ||
 |-
 | colspan = "2" | [[narcolepsy]] || [[HLA-DR2|DR2]] || [[HLA-DR12|DR12]] || || 
 |- 
 | [[nephritis]],|| tubulointerstitial || [[HLA-DR1|DR1]] || || || 
 |- 
 | [[nephropathy]] || IgA-mediated || [[HLA-DR4|DR4]] || || || 
 |- 
 | colspan = "2" | polyglandular deficiency syndrome || [[HLA-DR5|DR5]] || || || 
 |-
 |rowspan = "2" | [[pemphigus]] || foliaceous  || [[HLA-DR1|DR1]]  || || || 
 |- 
 | vulgaris || [[HLA-DR4|DR4]]  || || || 
 |- 
 | [[psoriasis]]  || vulgaris ||[[HLA-DR1|DR1]] ||[[HLA-DR7|DR7]]   || ||  
 |- 
 | papillomatosis, || respiratory ||[[HLA-DR1|DR1]]  || || || 
 |- 
 | [[sarcoidosis]] || non-chronic || [[HLA-DR17|DR17]] || [[HLA-DR52|DR52]] || || 
 |-
 | rowspan = "4" | [[sclerosis]], || mulitple || [[HLA-DR2|DR2]] || [[HLA-DR15|DR15]]  || [[HLA-DR53|DR53]] || 
 |- 
 | "bout onset" multiple || [[HLA-DR3|DR3]]  || || || 
 |- 
 | systemic || [[HLA-DR4|DR4]]  ||  [[HLA-DR11|DR11]] || [[HLA-DR16|DR16]] || [[HLA-DR52|DR52]]
 |-
 | vulval lichen || [[HLA-DR12|DR12]] || || || 
 |-
 | colspan = "2"| schizophrenia || [[HLA-DR1|DR1]] || || || 
 |- 
 | rowspan = "11" |susceptibility || [[leprosy]] || [[HLA-DR2|DR2]] || || || 
 |- 
 | [[tuberculosis]] || [[HLA-DR2|DR2]] || || || 
 |- 
 | ragweed Ra6 allergy || [[HLA-DR5|DR5]] || || || 
 |-  
 | asthma, mite sensitive || [[HLA-DR11|DR11]] || || || 
 |-
 | 2ndary infection, [[AIDS]] || [[HLA-DR3|DR3]] || || || 
 |-  
 | [[aspergillosis]] || [[HLA-DR15|DR15]] || || || 
 |-  
 | [[Kaposi's sarcoma]] || [[HLA-DR5|DR5]] || || || 
 |-  
 | [[thyroid carcinoma]]s || [[HLA-DR8|DR8]] || [[HLA-DR11|DR11]]  || ||
 |-
 | ovarian/cervical cancer || [[HLA-DR10|DR10]] || [[HLA-DR11|DR11]]  || [[HLA-DR15|DR15]] || 
 |-
 | grape induced anaphylaxis || [[HLA-DR11|DR11]] || || || 
 |-
 | Chlamydia pneumoniae || [[HLA-DR52|DR52]] || || || 
 |- 
 | rowspan = "2" | [[thyroiditis]] || Hashimoto's || [[HLA-DR2|DR2]] || [[HLA-DR5|DR5]]|| || 
 |- 
 | [[Grave's disease|Grave's]] || [[HLA-DR3|DR3]] || [[HLA-DR17|DR17]] || [[HLA-DR52|DR52]] || 
 |- 
 | [[uveitis]]|| tubulointerstitial || [[HLA-DR1|DR1]] || || || 
 |- 
 |colspan = "6" | <sup>*</sup>references are provided on linked subpages
 |}

=External links=
* {{MeshName|HLA-DR+antigens}}
==References==
{{reflist}}
==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading 
| citations = 
*{{cite journal  | author=Bénichou S, Benmerah A |title=The HIV nef and the Kaposi-sarcoma-associated virus K3/K5 proteins: "parasites"of the endocytosis pathway |journal=Med Sci (Paris) |volume=19 |issue= 1 |pages= 100-6 |year= 2003 |pmid= 12836198 |doi=  }}
*{{cite journal  | author=Tolstrup M, Ostergaard L, Laursen AL, ''et al.'' |title=HIV/SIV escape from immune surveillance: focus on Nef. |journal=Curr. HIV Res. |volume=2 |issue= 2 |pages= 141-51 |year= 2004 |pmid= 15078178 |doi=  }}
*{{cite journal  | author=Anderson JL, Hope TJ |title=HIV accessory proteins and surviving the host cell. |journal=Current HIV/AIDS reports |volume=1 |issue= 1 |pages= 47-53 |year= 2005 |pmid= 16091223 |doi=  }}
*{{cite journal  | author=Li L, Li HS, Pauza CD, ''et al.'' |title=Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions. |journal=Cell Res. |volume=15 |issue= 11-12 |pages= 923-34 |year= 2006 |pmid= 16354571 |doi= 10.1038/sj.cr.7290370 }}
*{{cite journal  | author=Stove V, Verhasselt B |title=Modelling thymic HIV-1 Nef effects. |journal=Curr. HIV Res. |volume=4 |issue= 1 |pages= 57-64 |year= 2006 |pmid= 16454711 |doi=  }}
*{{cite journal  | author=Matsushima GK, Itoh-Lindstrom Y, Ting JP |title=Activation of the HLA-DRA gene in primary human T lymphocytes: novel usage of TATA and the X and Y promoter elements. |journal=Mol. Cell. Biol. |volume=12 |issue= 12 |pages= 5610-9 |year= 1992 |pmid= 1448091 |doi=  }}
*{{cite journal  | author=Schaiff WT, Hruska KA, McCourt DW, ''et al.'' |title=HLA-DR associates with specific stress proteins and is retained in the endoplasmic reticulum in invariant chain negative cells. |journal=J. Exp. Med. |volume=176 |issue= 3 |pages= 657-66 |year= 1992 |pmid= 1512535 |doi=  }}
*{{cite journal  | author=Piatier-Tonneau D, Gastinel LN, Amblard F, ''et al.'' |title=Interaction of CD4 with HLA class II antigens and HIV gp120. |journal=Immunogenetics |volume=34 |issue= 2 |pages= 121-8 |year= 1991 |pmid= 1869305 |doi=  }}
*{{cite journal  | author=Nong Y, Kandil O, Tobin EH, ''et al.'' |title=The HIV core protein p24 inhibits interferon-gamma-induced increase of HLA-DR and cytochrome b heavy chain mRNA levels in the human monocyte-like cell line THP1. |journal=Cell. Immunol. |volume=132 |issue= 1 |pages= 10-6 |year= 1991 |pmid= 1905983 |doi=  }}
*{{cite journal  | author=Rosenstein Y, Burakoff SJ, Herrmann SH |title=HIV-gp120 can block CD4-class II MHC-mediated adhesion. |journal=J. Immunol. |volume=144 |issue= 2 |pages= 526-31 |year= 1990 |pmid= 1967269 |doi=  }}
*{{cite journal  | author=Callahan KM, Fort MM, Obah EA, ''et al.'' |title=Genetic variability in HIV-1 gp120 affects interactions with HLA molecules and T cell receptor. |journal=J. Immunol. |volume=144 |issue= 9 |pages= 3341-6 |year= 1990 |pmid= 1970352 |doi=  }}
*{{cite journal  | author=Bowman MR, MacFerrin KD, Schreiber SL, Burakoff SJ |title=Identification and structural analysis of residues in the V1 region of CD4 involved in interaction with human immunodeficiency virus envelope glycoprotein gp120 and class II major histocompatibility complex molecules. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=87 |issue= 22 |pages= 9052-6 |year= 1991 |pmid= 1978941 |doi=  }}
*{{cite journal  | author=Koppelman B, Cresswell P |title=Rapid nonlysosomal degradation of assembled HLA class II glycoproteins incorporating a mutant DR alpha-chain. |journal=J. Immunol. |volume=145 |issue= 8 |pages= 2730-6 |year= 1990 |pmid= 2212658 |doi=  }}
*{{cite journal  | author=Clayton LK, Sieh M, Pious DA, Reinherz EL |title=Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding. |journal=Nature |volume=339 |issue= 6225 |pages= 548-51 |year= 1989 |pmid= 2543930 |doi= 10.1038/339548a0 }}
*{{cite journal  | author=Diamond DC, Sleckman BP, Gregory T, ''et al.'' |title=Inhibition of CD4+ T cell function by the HIV envelope protein, gp120. |journal=J. Immunol. |volume=141 |issue= 11 |pages= 3715-7 |year= 1988 |pmid= 2846691 |doi=  }}
*{{cite journal  | author=Tjernlund U, Scheynius A, Johansson C, ''et al.'' |title=T-cell response to purified protein derivative after removal of Langerhans' cells from epidermal cell suspensions containing keratinocytes expressing class II transplantation antigens. |journal=Scand. J. Immunol. |volume=28 |issue= 6 |pages= 667-73 |year= 1989 |pmid= 3266023 |doi=  }}
*{{cite journal  | author=Andrieu JM, Even P, Venet A |title=AIDS and related syndromes as a viral-induced autoimmune disease of the immune system: an anti-MHC II disorder. Therapeutic implications. |journal=AIDS research |volume=2 |issue= 3 |pages= 163-74 |year= 1986 |pmid= 3489470 |doi=  }}
*{{cite journal  | author=Das HK, Lawrance SK, Weissman SM |title=Structure and nucleotide sequence of the heavy chain gene of HLA-DR. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=80 |issue= 12 |pages= 3543-7 |year= 1983 |pmid= 6304715 |doi=  }}
*{{cite journal  | author=Schamboeck A, Korman AJ, Kamb A, Strominger JL |title=Organization of the transcriptional unit of a human class II histocompatibility antigen: HLA-DR heavy chain. |journal=Nucleic Acids Res. |volume=11 |issue= 24 |pages= 8663-75 |year= 1984 |pmid= 6324094 |doi=  }}
*{{cite journal  | author=Das HK, Biro PA, Cohen SN, ''et al.'' |title=Use of synthetic oligonucleotide probes complementary to genes for human HLA-DR alpha and beta as extension primers for the isolation of 5'-specific genomic clones. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=80 |issue= 6 |pages= 1531-5 |year= 1983 |pmid= 6403940 |doi=  }}
}}
{{refend}}


{{Surface antigens}}
{{DR serotypes}}
[[Category:HLA-DR haplotypes|0]]
[[Category:Human MHC mediated diseases|R]]
[[Category:Genes on chromosome 6|H]]
[[Category:MHC Class II]]
{{WikiDoc Sources}}