View source for HLA-A3

{{Short description|Human leukocyte antigen serotype}}
{{see also|History and naming of human leukocyte antigens}}
{{Technical|date=May 2017}}
{{Infobox monoisoform
| isoformgroup  = HLA-A3
| polymer_type  = [[MHC Class I]], [[HLA-A|A]] cell surface antigen
| image         = Illustration_HLA-A.png
| protein_type  = [[transmembrane receptor]]/[[ligand]]
| structure     = αβ [[heterodimer]]
| subunit_genes = [[HLA-A]]*03--, [[Beta-2 microglobulin|β<sub>2</sub>-microglobulin]]
| linkout       = HAwA
| alias         = HL-A3
| isoformCount  = 2
| subunit1      = allele
| nick1         = A3.1
| allele1a      = 03:01
| nick2         = A3.2
| allele2a      = 03:02
| rareIsoforms  = 1
| rnick1        = A3.5
| rallele1a     = 03:05
}}

'''HLA-A3''' (A3) is a [[human leukocyte antigen]] ''[[serotype]]'' within [[HLA-A]] serotype group. The serotype is determined by the antibody recognition of α<sup>3</sup> subset of HLA-A α-chains. For A3, the alpha, "A", chain are encoded by the HLA-A{{color|DarkGreen|*03}} allele group and the β-chain are encoded by [[Beta-2 microglobulin|B2M]] [[wikt:locus|locus]].<ref name="pmid77067">{{cite journal |vauthors=Arce-Gomez B, Jones EA, Barnstable CJ, Solomon E, Bodmer WF |title=The genetic control of HLA-A and B antigens in somatic cell hybrids: requirement for beta2 microglobulin |journal=Tissue Antigens |volume=11 |issue=2 |pages=96–112 |date=February 1978 |pmid=77067 |doi= 10.1111/j.1399-0039.1978.tb01233.x}}</ref> This group currently is dominated by A*03:01.  A3 and A{{color|DarkGreen|*03}} are almost synonymous in meaning.
A3 is more common in Europe, it is part of the longest known multigene [[haplotype]], A3~B7~DR15~DQ6.<ref name="pmid18193213">{{cite journal  |vauthors=Horton R, Gibson R, Coggill P, etal |title=Variation analysis and gene annotation of eight MHC haplotypes: the MHC Haplotype Project |journal=Immunogenetics |volume=60 |issue=1 |pages=1–18 |date=January 2008 |pmid=18193213 |pmc=2206249 |doi=10.1007/s00251-007-0262-2 }}</ref>

==Serotype==
{{Serotype
| color1      = #B0E0FF |color2=#E0F0FF | color3 = #F0F8FF
| gene        = A 
| type        = 3
| types       = 1
| allelegroup = 03
| alleles     = 3
| allele1     = :01  |type1alle1freq = 99  |N1 = 3504
| allele2     = :02  |type1alle2freq = 78  |N2 = 342
| allele3     = :05  |type1alle3freq = {{color|grey|20}}  |N3 = 5
}} 
A3 is primarily composed of A*03:01 and *03:02 which serotype well with anti-A3 antibodies. 
There are 26 non-synonymous variants of A*03, 4 nulls, and 22 protein variants.

===Associated diseases===
A3 serotype is a secondary risk factor for ''[[myasthenia gravis]]''<ref name = "mg">{{cite journal |vauthors=Machens A, Löliger C, Pichlmeier U, Emskötter T, Busch C, Izbicki J | title = Correlation of thymic pathology with HLA in myasthenia gravis. | journal = Clinical Immunology | volume = 91 | issue = 3 | pages = 296–301 | year = 1999 | pmid = 10370374 | doi = 10.1006/clim.1999.4710}}</ref> and lower CD8<sup>+</sup> levels in [[hemochromatosis]] patients.<ref>{{cite journal |vauthors=Barton J, Wiener H, Acton R, Go R | title = HLA haplotype A*03-B*07 in hemochromatosis probands with HFE C282Y homozygosity: frequency disparity in men and women and lack of association with severity of iron overload. | journal = Blood Cells Mol Dis | volume = 34 | issue = 1 | pages = 38–47 | year = 2005| pmid = 15607698 | doi = 10.1016/j.bcmd.2004.08.022}}</ref><ref>{{cite journal |vauthors=Cruz E, Vieira J, Almeida S, Lacerda R, Gartner A, Cardoso C, Alves H, Porto G | title = A study of 82 extended HLA haplotypes in HFE-C282Y homozygous hemochromatosis subjects: relationship to the genetic control of CD8+ T-lymphocyte numbers and severity of iron overload. | journal = BMC Med Genet | volume = 7| pages = 16 | year = 2006| pmid = 16509978 | doi = 10.1186/1471-2350-7-16 | pmc = 1413516 | doi-access = free }}</ref>  The HFE (Hemochromatosis) locus lies between A3 and B7 within the A3~DQ6 superhaplotype.<ref name="pmid18363869">{{cite journal |vauthors=Olsson KS, Ritter B, Hansson N, Chowdhury RR |title=HLA haplotype map of river valley populations with hemochromatosis traced through five centuries in Central Sweden |journal=Eur. J. Haematol. |volume=81 |issue=1 |pages=36–46 |date=July 2008 |pmid=18363869 |doi=10.1111/j.1600-0609.2008.01078.x |s2cid=30689398 |doi-access=free }}</ref>

===In HIV===
HLA-A3 selects HIV evolution for a mutation Gag KK9 epitope and results in a rapid decline in the CD8 T-cell response. CD8 T-cells are responsible for quickly killing HIV infected CD4+ cells.<ref name="pmid15194783">{{cite journal  |vauthors=Allen TM, Altfeld M, Yu XG, etal |title=Selection, transmission, and reversion of an antigen-processing cytotoxic T-lymphocyte escape mutation in human immunodeficiency virus type 1 infection |journal=J. Virol. |volume=78 |issue=13 |pages=7069–78 |date=July 2004 |pmid=15194783 |pmc=421658 |doi=10.1128/JVI.78.13.7069-7078.2004 }}</ref> This type of evolved response may not be specific for HLA-A3 and since HIV is capable of adapting quickly in situ to selective factors.

<br/>
{{clear}}

==Alleles==
{{AlleleFreq
| Placement = right
| Allele    = A*03:01
| Freq1     = 25.0  | People1 = Finland
| Freq2     = 20.5  | People2 = India Tamil Nadu Nadar
| Freq3     = 18.9  | People3 = Czech Republic
| Freq4     = 17.1  | People4 = Belgium
| Freq5     = 14.3  | People5 = Ireland Northern
| Freq6     = 13.8  | People6 = Australia New South Wales
| Freq7     = 13.8  | People7 = Georgia Svaneti Svans
| Freq8     = 13.8  | People8 = Georgia Tbilisi Georgian…
| Freq9     = 13.0  | People9 = Pakistan Burusho
| Freq10    = 12.0  | People10 = Cape Verde Northwestern I…
| Freq11    = 11.6  | People11 = Ireland South
| Freq12    = 11.6  | People12 = Romanian
| Freq13    = 11.0  | People13 = Croatia
| Freq14    = 10.8  | People14 = USA Caucasians (3)
| Freq15    = 9.7  | People15 = Italy North (1)
| Freq16    = 9.4  | People16 = USA African Americans (2)
| Freq17    = 9.3  | People17 = India Mumbai Marathas
| Freq18    = 9.0  | People18 = India West Bhils
| Freq19    = 9.0  | People19 = Portugal Centre
| Freq20    = 8.7  | People20 = Pakistan Pathan
| Freq21    = 8.6  | People21 = Cameroon Beti
| Freq22    = 7.8  | People22 = Cameroon Bamileke
| Freq23    = 7.5  | People23 = Pakistan Kalash
| Freq24    = 7.5  | People24 = Saudi Arabia Guraiat and …
| Freq25    = 7.3  | People25 = USA Hispanic
| Freq26    = 7.2  | People26 = India North Delhi
| Freq27    = 7.0  | People27 = Madeira
| Freq28    = 6.9  | People28 = Russia Tuva (2)
| Freq29    = 6.7  | People29 = Tunisia
| Freq30    = 6.7  | People30 = USA North American Native…
| Freq31    = 6.5  | People31 = Cape Verde Southeastern I…
| Freq32    = 6.4  | People32 = Azores Santa Maria and Sa…
| Freq33    = 6.3  | People33 = Pakistan Baloch
| Freq34    = 6.2  | People34 = Guinea Bissau
| Freq35    = 6.0  | People35 = Israel Arab Druse
| Freq36    = 6.0  | People36 = South African Natal Zulu
| Freq37    = 6.0  | People37 = USA South Texas Hispanics
| Freq38    = 5.8  | People38 = India North Hindus
| Freq39    = 5.8  | People39 = Zambia Lusaka
| Freq40    = 5.6  | People40 = Iran Baloch
| Freq41    = 5.5  | People41 = Uganda Kampala
| Freq42    = 5.2  | People42 = Jordan Amman
| Freq43    = 5.2  | People43 = Kenya 
| Freq44    = 5.1  | People44 = Brazil
| Freq45    = 5.1  | People45 = Oman
| Freq46    = 5.0  | People46 = Cameroon Pygmy Baka
| Freq47    = 5.0  | People47 = Georgia Tbilisi Kurds
| Freq48    = 4.8  | People48 = Sudanese
| Freq49    = 4.6  | People49 = Bulgaria
| Freq50    = 4.6  | People50 = Pakistan Brahui
| Freq51    = 4.5  | People51 = China Beijing
| Freq52    = 4.4  | People52 = Australia Indig. Cape Yor…
| Freq53    = 4.4  | People53 = China Inner Mongolia
| Freq54    = 4.4  | People54 = Mali Bandiagara
| Freq55    = 4.4  | People55 = Pakistan Sindhi
| Freq56    = 4.1  | People56 = China Qinghai Hui
| Freq57    = 4.0  | People57 = Zimbabwe Harare Shona
| Freq58    = 3.8  | People58 = Cameroon Sawa
| Freq59    = 3.8  | People59 = Senegal Niokholo Mandenka
| Freq60    = 3.6  | People60 = Kenya Luo
| Freq61    = 3.4  | People61 = Morocco Nador Metalsa Cla…
| Freq62    = 3.1  | People62 = Kenya Nandi
| Freq63    = 3.1  | People63 = Mex. Guadalajara Mestizos…
| Freq64    = 2.9  | People64 = China Guangzhou
| Freq65    = 2.9  | People65 = China North Han
| Freq66    = 2.9  | People66 = Mongolia Buriat
| Freq67    = 2.5  | People67 = China  Tibetans
| Freq68    = 2.5  | People68 = China Yunnan Nu
| Freq69    = 2.4  | People69 = Mexico Mestizos
| Freq70    = 2.0  | People70 = American Samoa
| Freq71    = 2.0  | People71 = Singapore Javanese Indone…
}}
{{AlleleFreq
| Placement = left
| Allele    = A*03:02
| Freq1     = 8.3  | People1 = Georgia Tbilisi Kurds
| Freq2     = 4.1  | People2 = Morocco Nador Metalsa Cla…
| Freq3     = 2.8  | People3 = Pakistan Karachi Parsi
| Freq4     = 2.5  | People4 = Israel Arab Druse
| Freq5     = 2.3  | People5 = India New Delhi
| Freq6     = 2.3  | People6 = Sudanese
| Freq7     = 2.2  | People7 = India North Delhi
| Freq8     = 2.0  | People8 = India West Coast Parsis
| Freq9     = 2.0  | People9 = Portugal Centre
| Freq10    = 1.7  | People10 = India Andhra Pradesh Goll…
| Freq11    = 1.7  | People11 = Pakistan Kalash
| Freq12    = 1.6  | People12 = Pakistan Baloch
| Freq13    = 1.4  | People13 = Georgia Tbilisi Georgian…
| Freq14    = 1.4  | People14 = Saudi Arabia Guraiat and …
| Freq15    = 1.3  | People15 = Oman
| Freq16    = 1.3  | People16 = Pakistan Sindhi
| Freq17    = 1.0  | People17 = India North Hindus
| Freq18    = 1.0  | People18 = Pakistan Pathan
| Freq19    = 1.0  | People19 = South Africa Natal Tamil
| Freq20    = 0.8  | People20 = USA South Texas Hispanics
}}

===Associated diseases===
A*03:01 modulates increased risk for [[multiple sclerosis]]<ref>{{cite journal |vauthors=Fogdell-Hahn A, Ligers A, Grønning M, Hillert J, Olerup O | title = Multiple sclerosis: a modifying influence of HLA class I genes in an HLA class II associated autoimmune disease. | journal = Tissue Antigens | volume = 55 | issue = 2 | pages = 140–8 | year = 2000 | pmid = 10746785 | doi = 10.1034/j.1399-0039.2000.550205.x}}</ref>

==A3~B haplotypes==
A3-B7 is part of the A3~DQ2 superhaplotype
A3-B8  (Romania, svanS) <br>
A3~B35 (Bulgaria, Croatia, E. Black Sea)<br>
A3~B55 (E. Black Sea)

===A3~Cw7~B7===

A3~B7 is bimodal in frequency in Europe with one node in Ireland and the other in Switzerland, relatively speaking Switzerland appears to be higher. A3~Cw7~B7 is one of the most common multigene haplotypes in the western world, particularly in Central and Eastern Europe.

A{{color|Purple|*03:01}} ~ C{{color|Green|*07:02}} ~ B{{color|Magenta|*07:02}} ~ DRB1{{color|Brown|*15:01}} ~ DQA1{{color|DarkOrchid|*01:02}} ~ DQB1{{color|DarkGreen|*06:02}}

{{clear|left}}

==References==
{{reflist}}

{{HLA-A serotypes}}

[[Category:HLA-A alleles|3]]