HLA-A3 explained
See also: History and naming of human leukocyte antigens.
| Isoformgroup: | HLA-A3 |
| Polymer Type: | MHC Class I, A cell surface antigen |
| Protein Type: | transmembrane receptor/ligand |
| Structure: | αβ heterodimer |
| Subunit Genes: | HLA-A
|
| 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 α3 subset of HLA-A α-chains. For A3, the alpha, "A", chain are encoded by the HLA-A allele group and the β-chain are encoded by B2M locus.[1] This group currently is dominated by A*03:01. A3 and A 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 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[3] and lower CD8+ levels in hemochromatosis patients.[4] [5] The HFE (Hemochromatosis) locus lies between A3 and B7 within the A3~DQ6 superhaplotype.[6]
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.[7] 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[8]
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 ~ C ~ B ~ DRB1 ~ DQA1 ~ DQB1
Notes and References
- Arce-Gomez B, Jones EA, Barnstable CJ, Solomon E, Bodmer WF . The genetic control of HLA-A and B antigens in somatic cell hybrids: requirement for beta2 microglobulin . Tissue Antigens . 11 . 2 . 96–112 . February 1978 . 77067 . 10.1111/j.1399-0039.1978.tb01233.x.
- Horton R, Gibson R, Coggill P, etal . Variation analysis and gene annotation of eight MHC haplotypes: the MHC Haplotype Project . Immunogenetics . 60 . 1 . 1–18 . January 2008 . 18193213 . 2206249 . 10.1007/s00251-007-0262-2 .
- Machens A, Löliger C, Pichlmeier U, Emskötter T, Busch C, Izbicki J . Correlation of thymic pathology with HLA in myasthenia gravis. . Clinical Immunology . 91 . 3 . 296–301 . 1999 . 10370374 . 10.1006/clim.1999.4710.
- Barton J, Wiener H, Acton R, Go R . 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 . 2005. 15607698 . 10.1016/j.bcmd.2004.08.022.
- Cruz E, Vieira J, Almeida S, Lacerda R, Gartner A, Cardoso C, Alves H, Porto G . 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 . 2006. 16509978 . 10.1186/1471-2350-7-16 . 1413516 . free .
- Olsson KS, Ritter B, Hansson N, Chowdhury RR . HLA haplotype map of river valley populations with hemochromatosis traced through five centuries in Central Sweden . Eur. J. Haematol. . 81 . 1 . 36–46 . July 2008 . 18363869 . 10.1111/j.1600-0609.2008.01078.x . 30689398 . free .
- Allen TM, Altfeld M, Yu XG, etal . 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 . July 2004 . 15194783 . 421658 . 10.1128/JVI.78.13.7069-7078.2004 .
- Fogdell-Hahn A, Ligers A, Grønning M, Hillert J, Olerup O . Multiple sclerosis: a modifying influence of HLA class I genes in an HLA class II associated autoimmune disease. . Tissue Antigens . 55 . 2 . 140–8 . 2000 . 10746785 . 10.1034/j.1399-0039.2000.550205.x.
