HLA-A3

HLA-A3

monoisoform
isoformgroup = HLA-A3
polymer_type = MHC Class I, A cell surface antigen



protein_type = transmembrane receptor/ligand
structure = αβ heterodimer
subunit_genes = HLA-A*03--, β2-microglobulin
linkout = HAwA
alias = HL-A3
isoformCount = 2
subunit1 = allele
nick1 = A3.1
allele1a = 0301
nick2 = A3.2
allele2a = 0302
rareIsoforms = 1
rnick1 = A3.5
rallele1a = 0305

HLA-A3 (A3) is a human leukocyte antigen "serotype" within HLA-A serotype group. The serotype is determined by the antibody recognition of α3 subset of HLA-A α-chains. For A3, the alpha, "A", chain are encoded by the HLA-A*03 allele group and the β-chain are encoded by B2M .cite journal |author=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 |year=1978 |month=February |pmid=77067 |doi= |url=] This group currently is dominated by A*0301. A3 and A*03 are almost synonymous in meaning.A3 is more common in Western Eurasia, it is part of the longest known multigene haplotype, A3-B7-DR15-DQ6.cite journal |author=Horton R, Gibson R, Coggill P, "et al" |title=Variation analysis and gene annotation of eight MHC haplotypes: the MHC Haplotype Project |journal=Immunogenetics |volume=60 |issue=1 |pages=1–18 |year=2008 |month=January |pmid=18193213 |pmc=2206249 |doi=10.1007/s00251-007-0262-2 |url=]

erotype

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 = 20 |N3 = 5
A3 is primarily composed of A*0301 and *0302 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",cite journal | author = Machens A, Löliger C, Pichlmeier U, Emskötter T, Busch C, Izbicki J | title = Correlation of thymic pathology with HLA in myasthenia gravis. | journal = Clin Immunol | volume = 91 | issue = 3 | pages = 296–301 | year = 1999 | pmid = 10370374 | doi = 10.1006/clim.1999.4710] lower CD8+ levels in hemochromatosis patients [cite journal | author = 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 = | pmid = 15607698 | doi = 10.1016/j.bcmd.2004.08.022] [cite journal | author = 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 | issue = | pages = 16 | year = | pmid = 16509978 | doi = 10.1186/1471-2350-7-16] The HFE (Hemochromatosis) locus lies between A3 and B7 within the A3::DQ6 superhaplotype.cite journal |author=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 |year=2008 |month=July |pmid=18363869 |doi=10.1111/j.1600-0609.2008.01078.x |url=]

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.cite journal |author=Allen TM, Altfeld M, Yu XG, "et al" |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 |year=2004 |month=July |pmid=15194783 |pmc=421658 |doi=10.1128/JVI.78.13.7069-7078.2004 |url=] 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.

Alleles

AlleleFreq
Placement = right
Allele = A*0301
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 Tibilisi 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 Africian 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 Tibilisi 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*0302
Freq1 = 8.3 | People1 = Georgia Tibilisi 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 Tibilisi 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*0301 modulates increased risk for Multiple Sclerosis [cite journal | author = 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]

A3-B haplotypes

A3-B7 is part of the A3::DQ2 superhaplotypeA3-B8 (Romania, svanS)
A3-B35 (Bulgaria, Croatia, E. Black Sea)
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*0301 : C*0702 : B*0702 : DRB1*1501 : DQA1*0102 : DQB1*0602


References


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