HLA-A3

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HLA-A3
(MHC Class I, A cell surface antigen)
Illustration HLA-A.png
HLA-A3
About
Proteintransmembrane receptor/ligand
Structureαβ heterodimer
SubunitsHLA-A*03--, β2-microglobulin
Older namesHL-A3
Subtypes
Subtype
allele
Available structures
A3.1 *0301
A3.2 *0302
Rare alleles
Subtype
allele
Available structures
A3.5 *0305
Alleles link-out to IMGT/HLA database at EBI

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 locus.[1] This group currently is dominated by A*0301. A3 and A*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.[2]

Serotype[edit]

A3 recognition of some HLA A*03 gene products[3]
A*03 A3 Sample
allele % size (N)
*0301 99 3504
*0302 78 342
*0305 20 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[edit]

A3 serotype is a secondary risk factor for myasthenia gravis[4] and lower CD8+ levels in hemochromatosis patients.[5][6] The HFE (Hemochromatosis) locus lies between A3 and B7 within the A3::DQ6 superhaplotype.[7]

In HIV[edit]

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.[8] 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[edit]

HLA A*0301 frequencies
Study populationFreq.
 (in %)[9]
Finland25.0
India Tamil Nadu Nadar20.5
Czech Republic18.9
Belgium17.1
Ireland Northern14.3
Australia New South Wales13.8
Georgia Svaneti Svans13.8
Georgia Tibilisi Georgian…13.8
Pakistan Burusho13.0
Cape Verde Northwestern I…12.0
Ireland South11.6
Romanian11.6
Croatia11.0
USA Caucasians (3)10.8
Italy North (1)9.7
USA African Americans (2)9.4
India Mumbai Marathas9.3
India West Bhils9.0
Portugal Centre9.0
Pakistan Pathan8.7
Cameroon Beti8.6
Cameroon Bamileke7.8
Pakistan Kalash7.5
Saudi Arabia Guraiat and …7.5
USA Hispanic7.3
India North Delhi7.2
Madeira7.0
Russia Tuva (2)6.9
Tunisia6.7
USA North American Native…6.7
Cape Verde Southeastern I…6.5
Azores Santa Maria and Sa…6.4
Pakistan Baloch6.3
Guinea Bissau6.2
Israel Arab Druse6.0
South African Natal Zulu6.0
USA South Texas Hispanics6.0
India North Hindus5.8
Zambia Lusaka5.8
Iran Baloch5.6
Uganda Kampala5.5
Jordan Amman5.2
Kenya5.2
Brazil5.1
Oman5.1
Cameroon Pygmy Baka5.0
Georgia Tibilisi Kurds5.0
Sudanese4.8
Bulgaria4.6
Pakistan Brahui4.6
China Beijing4.5
Australia Indig. Cape Yor…4.4
China Inner Mongolia4.4
Mali Bandiagara4.4
Pakistan Sindhi4.4
China Qinghai Hui4.1
Zimbabwe Harare Shona4.0
Cameroon Sawa3.8
Senegal Niokholo Mandenka3.8
Kenya Luo3.6
Morocco Nador Metalsa Cla…3.4
Kenya Nandi3.1
Mex. Guadalajara Mestizos…3.1
China Guangzhou2.9
China North Han2.9
Mongolia Buriat2.9
China Tibetans2.5
China Yunnan Nu2.5
Mexico Mestizos2.4
American Samoa2.0
Singapore Javanese Indone…2.0
Allele frequencies presented, only
HLA A*0302 frequencies
Study populationFreq.
 (in %)[9]
Georgia Tibilisi Kurds8.3
Morocco Nador Metalsa Cla…4.1
Pakistan Karachi Parsi2.8
Israel Arab Druse2.5
India New Delhi2.3
Sudanese2.3
India North Delhi2.2
India West Coast Parsis2.0
Portugal Centre2.0
India Andhra Pradesh Goll…1.7
Pakistan Kalash1.7
Pakistan Baloch1.6
Georgia Tibilisi Georgian…1.4
Saudi Arabia Guraiat and …1.4
Oman1.3
Pakistan Sindhi1.3
India North Hindus1.0
Pakistan Pathan1.0
South Africa Natal Tamil1.0
USA South Texas Hispanics0.8
Allele frequencies presented, only

Associated diseases[edit]

A*0301 modulates increased risk for multiple sclerosis[10]

A3-B haplotypes[edit]

A3-B7 is part of the A3::DQ2 superhaplotype A3-B8 (Romania, svanS)
A3-B35 (Bulgaria, Croatia, E. Black Sea)
A3-B55 (E. Black Sea)

A3-Cw7-B7[edit]

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[edit]

  1. ^ Arce-Gomez B, Jones EA, Barnstable CJ, Solomon E, Bodmer WF (February 1978). "The genetic control of HLA-A and B antigens in somatic cell hybrids: requirement for beta2 microglobulin". Tissue Antigens. 11 (2): 96–112. doi:10.1111/j.1399-0039.1978.tb01233.x. PMID 77067.
  2. ^ Horton R, Gibson R, Coggill P, et al. (January 2008). "Variation analysis and gene annotation of eight MHC haplotypes: the MHC Haplotype Project". Immunogenetics. 60 (1): 1–18. doi:10.1007/s00251-007-0262-2. PMC 2206249. PMID 18193213.
  3. ^ Allele Query Form IMGT/HLA - European Bioinformatics Institute
  4. ^ Machens A, Löliger C, Pichlmeier U, Emskötter T, Busch C, Izbicki J (1999). "Correlation of thymic pathology with HLA in myasthenia gravis". Clin Immunol. 91 (3): 296–301. doi:10.1006/clim.1999.4710. PMID 10370374.
  5. ^ Barton J, Wiener H, Acton R, Go R (2005). "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". Blood Cells Mol Dis. 34 (1): 38–47. doi:10.1016/j.bcmd.2004.08.022. PMID 15607698.
  6. ^ Cruz E, Vieira J, Almeida S, Lacerda R, Gartner A, Cardoso C, Alves H, Porto G (2006). "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". BMC Med Genet. 7: 16. doi:10.1186/1471-2350-7-16. PMC 1413516. PMID 16509978.
  7. ^ Olsson KS, Ritter B, Hansson N, Chowdhury RR (July 2008). "HLA haplotype map of river valley populations with hemochromatosis traced through five centuries in Central Sweden". Eur. J. Haematol. 81 (1): 36–46. doi:10.1111/j.1600-0609.2008.01078.x. PMID 18363869.
  8. ^ Allen TM, Altfeld M, Yu XG, et al. (July 2004). "Selection, transmission, and reversion of an antigen-processing cytotoxic T-lymphocyte escape mutation in human immunodeficiency virus type 1 infection". J. Virol. 78 (13): 7069–78. doi:10.1128/JVI.78.13.7069-7078.2004. PMC 421658. PMID 15194783.
  9. ^ a b Middleton D, Menchaca L, Rood H, Komerofsky R (2003). "New allele frequency database: http://www.allelefrequencies.net". Tissue Antigens. 61 (5): 403–7. doi:10.1034/j.1399-0039.2003.00062.x. PMID 12753660.
  10. ^ Fogdell-Hahn A, Ligers A, Grønning M, Hillert J, Olerup O (2000). "Multiple sclerosis: a modifying influence of HLA class I genes in an HLA class II associated autoimmune disease". Tissue Antigens. 55 (2): 140–8. doi:10.1034/j.1399-0039.2000.550205.x. PMID 10746785.