HLA-A3

HLA-A3
(MHC Class I, A cell surface antigen)
HLA-A3
-
Protein transmembrane receptor/ligand
Structure αβ heterodimer
Subunits HLA-A*03--, β2-microglobulin
Older names "HL-A3"
-
subtype allele Available structures
A3.1 *0301
A3.2 *0302
rare alleles
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.

Further information: HLA serotypes explained

A3 is more common in Western Eurasia, it is part of the longest known multigene haplotype, A3-B7-DR15-DQ6.[2]

Contents

Serotype

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

A3 serotype is a secondary risk factor for myasthenia gravis,[4] 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

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

HLA A*0301 frequencies
 Study population  Freq.
 (in %)[9]
 Finland   25.0
 India Tamil Nadu Nadar   20.5
 Czech Republic   18.9
 Belgium   17.1
 Ireland Northern   14.3
 Australia New South Wales   13.8
 Georgia Svaneti Svans   13.8
 Georgia Tibilisi Georgian…   13.8
 Pakistan Burusho   13.0
 Cape Verde Northwestern I…   12.0
 Ireland South   11.6
 Romanian   11.6
 Croatia   11.0
 USA Caucasians (3)   10.8
 Italy North (1)   9.7
 USA African Americans (2)   9.4
 India Mumbai Marathas   9.3
 India West Bhils   9.0
 Portugal Centre   9.0
 Pakistan Pathan   8.7
 Cameroon Beti   8.6
 Cameroon Bamileke   7.8
 Pakistan Kalash   7.5
 Saudi Arabia Guraiat and …   7.5
 USA Hispanic   7.3
 India North Delhi   7.2
 Madeira   7.0
 Russia Tuva (2)   6.9
 Tunisia   6.7
 USA North American Native…   6.7
 Cape Verde Southeastern I…   6.5
 Azores Santa Maria and Sa…   6.4
 Pakistan Baloch   6.3
 Guinea Bissau   6.2
 Israel Arab Druse   6.0
 South Africian Natal Zulu   6.0
 USA South Texas Hispanics   6.0
 India North Hindus   5.8
 Zambia Lusaka   5.8
 Iran Baloch   5.6
 Uganda Kampala   5.5
 Jordan Amman   5.2
 Kenya   5.2
 Brazil   5.1
 Oman   5.1
 Cameroon Pygmy Baka   5.0
 Georgia Tibilisi Kurds   5.0
 Sudanese   4.8
 Bulgaria   4.6
 Pakistan Brahui   4.6
 China Beijing   4.5
 Australia Indig. Cape Yor…   4.4
 China Inner Mongolia   4.4
 Mali Bandiagara   4.4
 Pakistan Sindhi   4.4
 China Qinghai Hui   4.1
 Zimbabwe Harare Shona   4.0
 Cameroon Sawa   3.8
 Senegal Niokholo Mandenka   3.8
 Kenya Luo   3.6
 Morocco Nador Metalsa Cla…   3.4
 Kenya Nandi   3.1
 Mex. Guadalajara Mestizos…   3.1
 China Guangzhou   2.9
 China North Han   2.9
 Mongolia Buriat   2.9
 China Tibetans   2.5
 China Yunnan Nu   2.5
 Mexico Mestizos   2.4
 American Samoa   2.0
 Singapore Javanese Indone…   2.0
Allele frequencies presented, only
HLA A*0302 frequencies
 Study population  Freq.
 (in %)[9]
 Georgia Tibilisi Kurds   8.3
 Morocco Nador Metalsa Cla…   4.1
 Pakistan Karachi Parsi   2.8
 Israel Arab Druse   2.5
 India New Delhi   2.3
 Sudanese   2.3
 India North Delhi   2.2
 India West Coast Parsis   2.0
 Portugal Centre   2.0
 India Andhra Pradesh Goll…   1.7
 Pakistan Kalash   1.7
 Pakistan Baloch   1.6
 Georgia Tibilisi Georgian…   1.4
 Saudi Arabia Guraiat and …   1.4
 Oman   1.3
 Pakistan Sindhi   1.3
 India North Hindus   1.0
 Pakistan Pathan   1.0
 South Africa Natal Tamil   1.0
 USA South Texas Hispanics   0.8
Allele frequencies presented, only

Associated diseases

A*0301 modulates increased risk for Multiple Sclerosis[10]

A3-B haplotypes

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

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

  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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2206249. 
  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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1413516. 
  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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=421658. 
  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. 

HLA-A · A1 · A2 · A3 · A9 (A23 · A24) · A10 (A25 · A26 · A34 · A43 · A66) · A11 · A19 (A29 · A30 · A31 · A32 · A33 · A74) · A28 (A68 · A69) · A36 · A80