See also: History and naming of human leukocyte antigens

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*03:01. 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

A3 recognition of some HLA A*03 gene products[3]
A*03 A3 Sample
allele % size (N)
*03:01 99 3504
*03:02 78 342
*03:05 20 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[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

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

Associated diseases

A*03:01 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*03:01 ~ C*07:02 ~ B*07:02 ~ DRB1*15:01 ~ DQA1*01:02 ~ DQB1*06:02

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.
  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". Clinical Immunology. 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. S2CID 30689398.
  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): 403–407. 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.
Allikas: http://en.wikipedia.org/wiki/HLA-A3
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