HLA-A11

HLA-A11 (A11) is a human leukocyte antigen serotype within HLA-A "A" serotype group. The serotype is determined by the antibody recognition of α11 subset of HLA-A α-chains. For A11, the alpha "A" chain are encoded by the HLA-A*11 allele group and the β-chain are encoded by B2M locus.[1] This group currently is dominated by A*1101. A11 and A*11 are almost synonymous in meaning. A11 is more common in East Asia than elsewhere, it is part of several long haplotypes that appear to have been frequent in the ancient peoples of Asia.[2]

HLA-A11
(MHC Class I, A cell surface antigen)
Rendering of A11 (A*1101-B2M) in complex with HBV peptide homologue2HN7 HLA-A11 'alpha chain' (Cyan), β2-microglobulin (Rose), HBV peptide (yellow).
About
Proteintransmembrane receptor/ligand
Structureαβ heterodimer
SubunitsHLA-A*11--, β2-microglobulin
Older namesHL-A11
Subtypes
Subtype
allele
Available structures
A11E, A11.1 *1101 2hn7, 1x7q, 1qvo, 1q94
A11K, A11.2 *1102
Rare alleles
Subtype
allele
Available structures
A11.3 *1103
A11.4 *1104
Alleles link-out to IMGT/HLA database at EBI

Serotype

A11 recognition of some HLA A*11 gene products[3]
A*11 A11 Sample
allele % size (N)
*1101992530
*11027642
*11038318
*1104606

Serotyping of A11 demonstrates better recognition of the *1101 gene products and poorer recognition of other A*11 gene products. There are ~40 recognized alleles of A*11. There is only one null classified as A11.

In infectious disease

Associations have been observed between A11 and familial otosclerosis,[4][5] pulmonary tuberculosis,[6] leprosy,[7] and cytomegalovirus infection with epilepsy.[8] These and other studies suggest an involvement between A11 and secondary effects of certain herpes virus infections. A11 was also found increase in supraglottic cancer with poor 3 year survival.[9] In osteosarcoma A11 was found elevated.[10]

There is a strong association between anti-depressant induced hepatitis and HLA-A11.[11] In autoimmune hepatitis, A11 has a synergistic effect, acting together with DR4 and DR3 to increase the odds of disease to over 300.[12]

A11 is also part of a haplotype A11-Cw4-B35-DR1-DQ1 that is a second factor in the rapid progression of HIV.[13] The involvement of non-Hodgkin's lymphoma primarily as a result of Epstein-Barr virus reinfection does not appear to be a cause in this acceleration.[14]

Epstein–Barr virus anomaly

There are at least a couple of forms of lymphoproliferative diseases that appear to arise from unresolved Epstein–Barr virus infection. Examination of the virus itself has led to the discovery of strains that can all but turn off the A11-mediated class I response to the virus in A11 enriched peoples (see tables below). This ability to turn off the immune system and for the virus to remain active is a factor in carcinogenesis. Early studies of A serotypes revealed and association of A11 with Hodgkin's lymphoma and recent studies have shown a complex involvement of Epstein-Barr virus infection as a consequence of low A11 control over infection.[15][16]

Burkitt's lymphoma eventually lead to the discovery of the virus, however this disease is more evident in Africa. An involvement in cytotoxic T-lymphocytes down-regulation in Burkitt's lymphoma was subsequently discovered,[17][18] More recent studies show A11 is down-regulated, and that other genetic defects are a likely cause.[19] The ability to present EB virus antigens revealed a defect in the process after antigen process but before TAP1 involvement.[20] Other studies indicated that peptides bind A11 in delivery to the cell surface for CTL screening, but fall off, and are destroyed intracellularly.[21] However, A3 and A11 can process and load antigens even when proteosome activity is diminished suggesting an alternative mechanism for loading which may benefit in recovery from some disease but impair recovery of others.

It appears that these and other viruses have learned to exploit some defect in the region surrounding A11 that allows the near complete shut-down of gene expression. Oddly, in Africa A11 is at very low frequencies, and homozygotes are rare, suggesting that other genetic susceptibilities may exist that steer the virus toward Burkitt's lymphoma.

Alleles

HLA A*1101 frequencies
Study populationFreq.
 (in %)[22]
Papua New Guinea Madang63.6
PNG West Schrader Ranges55.0
Taiwan Hakka40.0
PNG Wosera38.5
ChinaYunnan Naxi38.0
Taiwan Tao36.0
China Guangxi Maonan35.2
China Guangzhou33.8
Taiwan Minnan (1)30.9
Thailand29.9
China Wuhan29.3
Taiwan Pazeh28.2
China South Han27.7
Thailand Northeast27.1
Singapore Chinese26.5
Taiwanese of Middle China…26.2
PNG New Britain Rabaul26.0
Pakistan Brahui25.2
Australia Indig. Groote E…24.0
India New Delhi23.5
USA Asian23.0
Pakistan Baloch22.2
Taiwan Thao21.7
China, Shandong, Linqu Co…20.4
Pakistan Sindhi19.6
Australia Indig. Cape Yor…18.0
PNG Karimui Plateau17.9
Singapore Riau Malay17.7
Taiwan Siraya17.6
China Beijing16.4
Pakistan Pathan16.3
China Inner Mongolia16.2
American Samoa16.0
Spain Basque Arratia Vall…16.0
China Qinghai Hui15.9
Russia Murmansk Saomi14.0
Singapore Javanese Indone…14.0
New Caledonia13.1
Japan Aichi12.7
Georgia Svaneti Svans12.5
India North Hindus12.5
Pakistan Burusho12.5
China Yunnan Han (2)12.3
India Mumbai Marathas12.3
China Harbin N. Korean12.1
India Andhra Pradesh Goll…11.9
Taiwan Saisiat11.8
Oman11.4
Israel Arab Druse11.0
South Korea (3)10.8
Taiwan Tsou10.8
Mongolia Khoton Tarialan10.7
Sri Lanka Colombo Sinhale…10.4
Georgia Tbilisi Kurds10.0
Mongolia Khalkha10.0
Australia Indig. Kimberly9.7
India North Delhi9.4
Japan Hyogo9.4
Spain North Cabuernigo8.9
Saudi Arabia8.7
Russia Tuva (2)8.7
Spain North Cantabrian8.4
Japan Central8.2
Romanian8.2
Greece North8.0
Ireland Northern8.0
Taiwan Atayal8.0
Jordan Amman7.9
Italy North (1)7.7
Italy Sardinia (3)7.7
Australia Indig. Yuendumu7.6
Mongolia Tsaatan7.6
USA Caucasians (3)7.4
Bulgaria7.3
Taiwan Taroko7.3
Philippines Ivatan7.0
USA Caucasian Bethesda7.0
Portugal Centre (2)6.8
Australia New South Wales6.7
Morocco6.7
USA Hawaii Okinawa6.7
Wales6.6
Serbia6.5
Georgia Tbilisi Georgian…6.2
Ireland South6.2
Algeria(1)6.2
Brazil6.1
Spain Basque Gipuzkoa Pro…6.1
Turkey (2)6.1
Russia Northwest6.0
Portugal South pop25.9
England Newcastle5.7
Italy North Pavia5.6
Israeli Jews5.4
Sweden Stockholm5.1
Finland5.0
Macedonia (4)4.9
Italy Bergamo4.8
Morocco Berber Nador Meta…4.8
Allele frequencies presented, only
HLA A*1102 frequencies
Study populationFreq.
 (in %)[22]
Taiwan Saisiat12.7
Taiwan Pazeh10.9
Taiwan Ami8.7
Taiwan Puyuma7.0
Taiwan Siraya6.9
China Guangxi Maonan6.5
Taiwan Atayal5.2
Philippines Ivatan5.0
Ch. Guangdong Meizhou Han4.6
Taiwan Hakka4.5
Hong Kong Chinese4.0
Taiwan Minnan (1)3.9
Thailand3.5
Singapore Chinese3.0
Taiwan Tao3.0
Taiwan Tsou2.9
China Beijing Shijiazhuan…2.0
Italy North pop 11.9
Taiwan Taroko1.8
China Inner Mongolia1.0
India West Coast Parsis1.0
Taiwan Bunun1.0
China Qinghai Hui0.9
China Yunnan Lisu0.6
Japan (3)0.2
Allele frequencies presented, only
HLA A*1103 frequencies
Study populationFreq.
 (in %)[22]
China Yunnan Lisu5.1
China Yunnan Nu3.8
China Beijing Shijiazhuan…0.2
Allele frequencies presented, only
HLA A*1104 frequencies
Study populationFreq.
 (in %)[22]
Georgia Svaneti Svans1.3
Singapore Riau Malay1.2
American Samoa1.0
India North Hindus1.0
Israel Ashkenazi and Non …0.4
China Beijing Shijiazhuan…0.2
Allele frequencies presented, only

Disease associations

A*1104 is associated with increased risk for cervical neoplasia resulting from human papillomavirus infection[23]

A11-B haplotypes

A11-B13

  • A11-Cw2-B13 (Li)
  • A11-Cw9-B13 (Southern China & SE Asia)
  • A11-C10-B13 Buyi
  • A11-CBL-B13 Northern China

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. de Campos-Lima PO, Levitsky V, Brooks J, et al. (April 1994). "T cell responses and virus evolution: loss of HLA A11-restricted CTL epitopes in Epstein-Barr virus isolates from highly A11-positive populations by selective mutation of anchor residues". J. Exp. Med. 179 (4): 1297–305. doi:10.1084/jem.179.4.1297. PMC 2191457. PMID 7511684.
  3. Allele Query Form IMGT/HLA - European Bioinformatics Institute
  4. Gregoriadis S, Zervas J, Varletzidis E, Toubis M, Pantazopoulos P, Fessas P (December 1982). "HLA antigens and otosclerosis. A possible new genetic factor". Arch Otolaryngol. 108 (12): 769–71. doi:10.1001/archotol.1982.00790600013004. PMID 6983341.
  5. Singhal SK, Mann SB, Datta U, Panda NK, Gupta AK (1999). "Genetic correlation in otosclerosis". Am J Otolaryngol. 20 (2): 102–5. doi:10.1016/S0196-0709(99)90019-4. PMID 10203160.
  6. Xu XP, Li SB, Wang CY, Li QH (June 1986). "Study on the association of HLA with pulmonary tuberculosis". Immunol. Invest. 15 (4): 327–32. doi:10.3109/08820138609052951. PMID 3759149.
  7. Kim SJ, Choi IH, Dahlberg S, Nisperos B, Kim JD, Hansen JA (March 1987). "HLA and leprosy in Koreans". Tissue Antigens. 29 (3): 146–53. doi:10.1111/j.1399-0039.1987.tb01567.x. PMID 3603547.
  8. Iannetti P, Morellini M, Raucci U, Cappellacci S (1988). "HLA antigens, epilepsy and cytomegalovirus infection". Brain Dev. 10 (4): 256–8. doi:10.1016/s0387-7604(88)80008-1. PMID 2851270. S2CID 4706944.
  9. Konieczna A, Turowski G (1993). "HLA-ABC antigens in supraglottic cancer patients and their relationship with incidence and survival". Mater Med Pol. 25 (2): 73–9. PMID 8072312.
  10. Barona P, Sierrasesúmaga L, Antillón F, Villa-Elízaga I (1993). "Study of HLA antigens in patients with osteosarcoma". Hum. Hered. 43 (5): 311–4. doi:10.1159/000154149. PMID 8406520.
  11. Berson A, Fréneaux E, Larrey D, et al. (March 1994). "Possible role of HLA in hepatotoxicity. An exploratory study in 71 patients with drug-induced idiosyncratic hepatitis". J. Hepatol. 20 (3): 336–42. doi:10.1016/S0168-8278(94)80004-9. PMID 8014443.
  12. Marcos Y, Fainboim HA, Capucchio M, et al. (June 1994). "Two-locus involvement in the association of human leukocyte antigen with the extrahepatic manifestations of autoimmune chronic active hepatitis". Hepatology. 19 (6): 1371–4. doi:10.1016/0270-9139(94)90230-5. PMID 8188167.
  13. Roger M (June 1998). "Influence of host genes on HIV-1 disease progression". FASEB J. 12 (9): 625–32. doi:10.1096/fasebj.12.9.625. PMID 9619442. S2CID 7210509.
  14. Chu PG, Chang KL, Chen WG, et al. (September 1999). "Epstein-Barr virus (EBV) nuclear antigen (EBNA)-4 mutation in EBV-associated malignancies in three different populations". Am. J. Pathol. 155 (3): 941–7. doi:10.1016/S0002-9440(10)65193-0. PMC 1866909. PMID 10487851.
  15. Forbes JF, Morris PJ (May 1972). "Analysis of HL-A antigens in patients with Hodgkin's disease and their families". J. Clin. Invest. 51 (5): 1156–63. doi:10.1172/JCI106908. PMC 292245. PMID 5020429.
  16. Dolcetti R, Frisan T, Sjöberg J, et al. (August 1995). "Identification and characterization of an Epstein-Barr virus-specific T-cell response in the pathologic tissue of a patient with Hodgkin's disease". Cancer Res. 55 (16): 3675–81. PMID 7627978.
  17. Masucci MG, Torsteindottir S, Colombani J, Brautbar C, Klein E, Klein G (July 1987). "Down-regulation of class I HLA antigens and of the Epstein-Barr virus-encoded latent membrane protein in Burkitt lymphoma lines". Proc. Natl. Acad. Sci. U.S.A. 84 (13): 4567–71. doi:10.1073/pnas.84.13.4567. PMC 305131. PMID 3037521.
  18. Gavioli R, De Campos-Lima PO, Kurilla MG, Kieff E, Klein G, Masucci MG (July 1992). "Recognition of the Epstein-Barr virus-encoded nuclear antigens EBNA-4 and EBNA-6 by HLA-A11-restricted cytotoxic T lymphocytes: implications for down-regulation of HLA-A11 in Burkitt lymphoma". Proc. Natl. Acad. Sci. U.S.A. 89 (13): 5862–6. doi:10.1073/pnas.89.13.5862. PMC 49397. PMID 1321426.
  19. Imreh MP, Zhang QJ, de Campos-Lima PO, et al. (July 1995). "Mechanisms of allele-selective down-regulation of HLA class I in Burkitt's lymphoma". Int. J. Cancer. 62 (1): 90–6. doi:10.1002/ijc.2910620117. PMID 7601573. S2CID 25993298.
  20. Frisan T, Zhang QJ, Levitskaya J, Coram M, Kurilla MG, Masucci MG (October 1996). "Defective presentation of MHC class I-restricted cytotoxic T-cell epitopes in Burkitt's lymphoma cells". Int. J. Cancer. 68 (2): 251–8. doi:10.1002/(SICI)1097-0215(19961009)68:2<251::AID-IJC19>3.0.CO;2-D. PMID 8900437.
  21. Levitsky V, Zhang QJ, Levitskaya J, Kurilla MG, Masucci MG (December 1997). "Natural variants of the immunodominant HLA A11-restricted CTL epitope of the EBV nuclear antigen-4 are nonimmunogenic due to intracellular dissociation from MHC class I:peptide complexes". J. Immunol. 159 (11): 5383–90. PMID 9548478.
  22. 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.
  23. Chan D, Cheung T, Tam A, Cheung J, Yim S, Lo K, Siu N, Zhou D, Chan P (2005). "Risk association between human leukocyte antigen-A allele and high-risk human papillomavirus infection for cervical neoplasia in Chinese women". J Infect Dis. 192 (10): 1749–56. doi:10.1086/497342. PMID 16235173.
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