HLA-A11

monoisoform
isoformgroup = HLA-A11
polymer_type = MHC Class I, A cell surface antigen


image_source = Rendering of A11 (A*1101-B2M) in complex with HBV peptide homologuePDB2|2HN7 HLA-A11 'alpha chain' (Cyan), β₂-microglobulin (Rose), HBV peptide (yellow).
protein_type = transmembrane receptor/ligand
structure = αβ heterodimer
subunit_genes = HLA-A*11--, β₂-microglobulin
alias = HL-A11
linkout = HAwA
isoformCount = 2
subunit1 = allele
nick1 = A11E, A11.1
allele1a = 1101
images1 = PDB2|2hn7, PDB2|1x7q, PDB2|1qvo, PDB2|1q94
nick2 = A11K, A11.2
allele2a = 1102
rareIsoforms = 2
rnick1 = A11.3
rallele1a = 1103
rnick2 = A11.4
rallele2a = 1104

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 .cite journal |author=Arce-Gomez B, Jones EA, Barnstable CJ, Solomon E, Bodmer WF |title=The genetic control of HLA-A and B antigens in somatic cell hybrids: requirement for beta2 microglobulin |journal=Tissue Antigens |volume=11 |issue=2 |pages=96–112 |year=1978 |month=February |pmid=77067 |doi= |url=] 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 a several long haplotypes that appear to have been frequent in the ancient peoples of Asia.cite journal |author=de Campos-Lima PO, Levitsky V, Brooks J, "et al" |title=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 |journal=J. Exp. Med. |volume=179 |issue=4 |pages=1297–305 |year=1994 |month=April |pmid=7511684 |pmc=2191457 |doi= |url=]

erotype

Serotype
color1=#B0E0FF |color2=#E0F0FF | color3 = #F0F8FF
gene = A
type = 11
types = 1
allelegroup = 11
alleles = 4
allele1 = 01 |type1alle1freq = 99 |N1 = 2530
allele2 = 02 |type1alle2freq = 76 |N2 = 42
allele3 = 03 |type1alle3freq = 83 |N3 = 18
allele4 = 04 |type1alle4freq = 60 |N4 = 6 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, cite journal |author=Gregoriadis S, Zervas J, Varletzidis E, Toubis M, Pantazopoulos P, Fessas P |title=HLA antigens and otosclerosis. A possible new genetic factor |journal=Arch Otolaryngol |volume=108 |issue=12 |pages=769–71 |year=1982 |month=December |pmid=6983341 |doi= |url=] cite journal |author=Singhal SK, Mann SB, Datta U, Panda NK, Gupta AK |title=Genetic correlation in otosclerosis |journal=Am J Otolaryngol |volume=20 |issue=2 |pages=102–5 |year=1999 |pmid=10203160 |doi= |url=] pulmonary tuberculosis,cite journal |author=Xu XP, Li SB, Wang CY, Li QH |title=Study on the association of HLA with pulmonary tuberculosis |journal=Immunol. Invest. |volume=15 |issue=4 |pages=327–32 |year=1986 |month=June |pmid=3759149 |doi= |url=] leprosy,cite journal |author=Kim SJ, Choi IH, Dahlberg S, Nisperos B, Kim JD, Hansen JA |title=HLA and leprosy in Koreans |journal=Tissue Antigens |volume=29 |issue=3 |pages=146–53 |year=1987 |month=March |pmid=3603547 |doi= |url=] and cytomegalovirus infection with epilepsy.cite journal |author=Iannetti P, Morellini M, Raucci U, Cappellacci S |title=HLA antigens, epilepsy and cytomegalovirus infection |journal=Brain Dev. |volume=10 |issue=4 |pages=256–8 |year=1988 |pmid=2851270 |doi= |url=] 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.cite journal |author=Konieczna A, Turowski G |title=HLA-ABC antigens in supraglottic cancer patients and their relationship with incidence and survival |journal=Mater Med Pol |volume=25 |issue=2 |pages=73–9 |year=1993 |pmid=8072312 |doi= |url=] In osteosarcoma A11 was found elevated.cite journal |author=Barona P, Sierrasesúmaga L, Antillón F, Villa-Elízaga I |title=Study of HLA antigens in patients with osteosarcoma |journal=Hum. Hered. |volume=43 |issue=5 |pages=311–4 |year=1993 |pmid=8406520 |doi= |url=]

There is a strong association between anti-depressant induced hepatitis and HLA-A11cite journal |author=Berson A, Fréneaux E, Larrey D, "et al" |title=Possible role of HLA in hepatotoxicity. An exploratory study in 71 patients with drug-induced idiosyncratic hepatitis |journal=J. Hepatol. |volume=20 |issue=3 |pages=336–42 |year=1994 |month=March |pmid=8014443 |doi= |url=] . In autoimmune hepatitis, A11 has a synergistic effect, acting together with DR4 and DR3 to increase the odds of disease to over 300.cite journal |author=Marcos Y, Fainboim HA, Capucchio M, "et al" |title=Two-locus involvement in the association of human leukocyte antigen with the extrahepatic manifestations of autoimmune chronic active hepatitis |journal=Hepatology |volume=19 |issue=6 |pages=1371–4 |year=1994 |month=June |pmid=8188167 |doi= |url=]

A11 is also part of a haplotype A11-Cw4-B35-DR1-DQ1 that is a second factor in the rapid progression of HIV.cite journal |author=Roger M |title=Influence of host genes on HIV-1 disease progression |journal=FASEB J. |volume=12 |issue=9 |pages=625–32 |year=1998 |month=June |pmid=9619442 |doi= |url=http://www.fasebj.org/cgi/pmidlookup?view=long&pmid=9619442] The involvement of non-Hodgkin's lymphoma primaruily as a a result of Epstein-Barr virus reinfection does not appear to be a cause in this acceleration.cite journal |author=Chu PG, Chang KL, Chen WG, "et al" |title=Epstein-Barr virus (EBV) nuclear antigen (EBNA)-4 mutation in EBV-associated malignancies in three different populations |journal=Am. J. Pathol. |volume=155 |issue=3 |pages=941–7 |year=1999 |month=September |pmid=10487851 |pmc=1866909 |doi= |url=http://ajp.amjpathol.org/cgi/pmidlookup?view=long&pmid=10487851]

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 lead 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.cite journal |author=Forbes JF, Morris PJ |title=Analysis of HL-A antigens in patients with Hodgkin's disease and their families |journal=J. Clin. Invest. |volume=51 |issue=5 |pages=1156–63 |year=1972 |month=May |pmid=5020429 |pmc=292245 |doi=10.1172/JCI106908 |url=] cite journal |author=Dolcetti R, Frisan T, Sjöberg J, "et al" |title=Identification and characterization of an Epstein-Barr virus-specific T-cell response in the pathologic tissue of a patient with Hodgkin's disease |journal=Cancer Res. |volume=55 |issue=16 |pages=3675–81 |year=1995 |month=August |pmid=7627978 |doi= |url=http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=7627978]

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,cite journal |author=Masucci MG, Torsteindottir S, Colombani J, Brautbar C, Klein E, Klein G |title=Down-regulation of class I HLA antigens and of the Epstein-Barr virus-encoded latent membrane protein in Burkitt lymphoma lines |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue=13 |pages=4567–71 |year=1987 |month=July |pmid=3037521 |pmc=305131 |doi= |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=3037521] cite journal |author=Gavioli R, De Campos-Lima PO, Kurilla MG, Kieff E, Klein G, Masucci MG |title=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 |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=89 |issue=13 |pages=5862–6 |year=1992 |month=July |pmid=1321426 |pmc=49397 |doi= |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=1321426] More recent studies show A11 is down-regulated, and that other genetic defects are a likely cause.cite journal |author=Imreh MP, Zhang QJ, de Campos-Lima PO, "et al" |title=Mechanisms of allele-selective down-regulation of HLA class I in Burkitt's lymphoma |journal=Int. J. Cancer |volume=62 |issue=1 |pages=90–6 |year=1995 |month=July |pmid=7601573 |doi= |url=] The ability to present EB virus antigens revealed a defect in the process after antigen process but before TAP1 involvement.cite journal |author=Frisan T, Zhang QJ, Levitskaya J, Coram M, Kurilla MG, Masucci MG |title=Defective presentation of MHC class I-restricted cytotoxic T-cell epitopes in Burkitt's lymphoma cells |journal=Int. J. Cancer |volume=68 |issue=2 |pages=251–8 |year=1996 |month=October |pmid=8900437 |doi=10.1002/(SICI)1097-0215(19961009)68:2<251::AID-IJC19>3.0.CO;2-D |url=] Other studies indicated that peptides bind A11 in delivery to the cell surface for CTL screening, but fall off, and are destroyed intracellularly.cite journal |author=Levitsky V, Zhang QJ, Levitskaya J, Kurilla MG, Masucci MG |title=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 |journal=J. Immunol. |volume=159 |issue=11 |pages=5383–90 |year=1997 |month=December |pmid=9548478 |doi= |url=http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=9548478] 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

AlleleFreq
Placement = right
Allele = A*1101
Freq1 = 63.6 | People1 = Papua New Guinea Madang
Freq2 = 55.0 | People2 = PNG West Schrader Ranges
Freq3 = 40.0 | People3 = Taiwan Hakka
Freq4 = 38.5 | People4 = PNG Wosera
Freq5 = 38.0 | People5 = ChinaYunnan Naxi
Freq6 = 36.0 | People6 = Taiwan Tao
Freq7 = 35.2 | People7 = China Guangxi Maonan
Freq8 = 33.8 | People8 = China Guangzhou
Freq9 = 30.9 | People9 = Taiwan Minnan (1)
Freq10 = 29.9 | People10 = Thailand
Freq11 = 29.3 | People11 = China Wuhan
Freq12 = 28.2 | People12 = Taiwan Pazeh
Freq13 = 27.7 | People13 = China South Han
Freq14 = 27.1 | People14 = Thailand Northeast
Freq15 = 26.5 | People15 = Singapore Chinese
Freq16 = 26.2 | People16 = Taiwanese of Middle China…
Freq17 = 26.0 | People17 = PNG New Britain Rabaul
Freq18 = 25.2 | People18 = Pakistan Brahui
Freq19 = 24.0 | People19 = Australia Indig. Groote E…
Freq20 = 23.5 | People20 = India New Delhi
Freq21 = 23.0 | People21 = USA Asian
Freq22 = 22.2 | People22 = Pakistan Baloch
Freq23 = 21.7 | People23 = Taiwan Thao
Freq24 = 20.4 | People24 = China, Shandong, Linqu Co…
Freq25 = 19.6 | People25 = Pakistan Sindhi
Freq26 = 18.0 | People26 = Australia Indig. Cape Yor…
Freq27 = 17.9 | People27 = PNG Karimui Plateau
Freq28 = 17.7 | People28 = Singapore Riau Malay
Freq29 = 17.6 | People29 = Taiwan Siraya
Freq30 = 16.4 | People30 = China Beijing
Freq31 = 16.3 | People31 = Pakistan Pathan
Freq32 = 16.2 | People32 = China Inner Mongolia
Freq33 = 16.0 | People33 = American Samoa
Freq34 = 16.0 | People34 = Spain Basque Arratia Vall…
Freq35 = 15.9 | People35 = China Qinghai Hui
Freq36 = 14.0 | People36 = Russia Murmansk Saomi
Freq37 = 14.0 | People37 = Singapore Javanese Indone…
Freq38 = 13.1 | People38 = New Caledonia
Freq39 = 12.7 | People39 = Japan Aichi
Freq40 = 12.5 | People40 = Georgia Svaneti Svans
Freq41 = 12.5 | People41 = India North Hindus
Freq42 = 12.5 | People42 = Pakistan Burusho
Freq43 = 12.3 | People43 = China Yunnan Han (2)
Freq44 = 12.3 | People44 = India Mumbai Marathas
Freq45 = 12.1 | People45 = China Harbin N. Korean
Freq46 = 11.9 | People46 = India Andhra Pradesh Goll…
Freq47 = 11.8 | People47 = Taiwan Saisiat
Freq48 = 11.4 | People48 = Oman
Freq49 = 11.0 | People49 = Israel Arab Druse
Freq50 = 10.8 | People50 = South Korea (3)
Freq51 = 10.8 | People51 = Taiwan Tsou
Freq52 = 10.7 | People52 = Mongolia Khoton Tarialan
Freq53 = 10.4 | People53 = Sri Lanka Colombo Sinhale…
Freq54 = 10.0 | People54 = Georgia Tibilisi Kurds
Freq55 = 10.0 | People55 = Mongolia Khalkha
Freq56 = 9.7 | People56 = Australia Indig. Kimberly
Freq57 = 9.4 | People57 = India North Delhi
Freq58 = 9.4 | People58 = Japan Hyogo
Freq59 = 8.9 | People59 = Spain North Cabuernigo
Freq60 = 8.7 | People60 = Saudi Arabia
Freq61 = 8.7 | People61 = Russia Tuva (2)
Freq62 = 8.4 | People62 = Spain North Cantabrian
Freq63 = 8.2 | People63 = Japan Central
Freq64 = 8.2 | People64 = Romanian
Freq65 = 8.0 | People65 = Greece North
Freq66 = 8.0 | People66 = Ireland Northern
Freq67 = 8.0 | People67 = Taiwan Atayal
Freq68 = 7.9 | People68 = Jordan Amman
Freq69 = 7.7 | People69 = Italy North (1)
Freq70 = 7.7 | People70 = Italy Sardinia (3)
Freq71 = 7.6 | People71 = Australia Indig. Yuendumu
Freq72 = 7.6 | People72 = Mongolia Tsaatan
Freq73 = 7.4 | People73 = USA Caucasians (3)
Freq74 = 7.3 | People74 = Bulgaria
Freq75 = 7.3 | People75 = Taiwan Taroko
Freq76 = 7.0 | People76 = Philippines Ivatan
Freq77 = 7.0 | People77 = USA Caucasian Bethesda
Freq78 = 6.8 | People78 = Portugal Centre (2)
Freq79 = 6.7 | People79 = Australia New South Wales
Freq80 = 6.7 | People80 = Morocco
Freq81 = 6.7 | People81 = USA Hawaii Okinawa
Freq82 = 6.6 | People82 = Wales
Freq83 = 6.5 | People83 = Serbia
Freq84 = 6.2 | People84 = Georgia Tibilisi Georgian…
Freq85 = 6.2 | People85 = Ireland South
Freq86 = 6.2 | People86 = Algeria(1)
Freq87 = 6.1 | People87 = Brazil
Freq88 = 6.1 | People88 = Spain Basque Gipuzkoa Pro…
Freq89 = 6.1 | People89 = Turkey (2)
Freq90 = 6.0 | People90 = Russia Northwest
Freq91 = 5.9 | People91 = Portugal South pop2
Freq92 = 5.7 | People92 = England Newcastle
Freq93 = 5.6 | People93 = Italy North Pavia
Freq94 = 5.4 | People94 = Israeli Jews
Freq95 = 5.1 | People95 = Sweden Stockholm
Freq96 = 5.0 | People96 = Finland
Freq97 = 4.9 | People97 = Macedonia (4)
Freq98 = 4.8 | People98 = Italy Bergamo
Freq99 = 4.8 | People99 = Morocco Berber Nador Meta…AlleleFreq
Placement = left
Allele = A*1102
Freq1 = 12.7 | People1 = Taiwan Saisiat
Freq2 = 10.9 | People2 = Taiwan Pazeh
Freq3 = 8.7 | People3 = Taiwan Ami
Freq4 = 7.0 | People4 = Taiwan Puyuma
Freq5 = 6.9 | People5 = Taiwan Siraya
Freq6 = 6.5 | People6 = China Guangxi Maonan
Freq7 = 5.2 | People7 = Taiwan Atayal
Freq8 = 5.0 | People8 = Philippines Ivatan
Freq9 = 4.6 | People9 = Ch. Guangdong Meizhou Han
Freq10 = 4.5 | People10 = Taiwan Hakka
Freq11 = 4.0 | People11 = Hong Kong Chinese
Freq12 = 3.9 | People12 = Taiwan Minnan (1)
Freq13 = 3.5 | People13 = Thailand
Freq14 = 3.0 | People14 = Singapore Chinese
Freq15 = 3.0 | People15 = Taiwan Tao
Freq16 = 2.9 | People16 = Taiwan Tsou
Freq17 = 2.0 | People17 = China Beijing Shijiazhuan…
Freq18 = 1.9 | People18 = Italy North pop 1
Freq19 = 1.8 | People19 = Taiwan Taroko
Freq20 = 1.0 | People20 = China Inner Mongolia
Freq21 = 1.0 | People21 = India West Coast Parsis
Freq22 = 1.0 | People22 = Taiwan Bunun
Freq23 = 0.9 | People23 = China Qinghai Hui
Freq24 = 0.6 | People24 = China Yunnan Lisu
Freq25 = 0.2 | People25 = Japan (3)AlleleFreq
Placement = left
Allele = A*1103
Freq1 = 5.1 | People1 = China Yunnan Lisu
Freq2 = 3.8 | People2 = China Yunnan Nu
Freq3 = 0.2 | People3 = China Beijing Shijiazhuan…AlleleFreq
Placement = left
Allele = A*1104
Freq1 = 1.3 | People1 = Georgia Svaneti Svans
Freq2 = 1.2 | People2 = Singapore Riau Malay
Freq3 = 1.0 | People3 = American Samoa
Freq4 = 1.0 | People4 = India North Hindus
Freq5 = 0.4 | People5 = Israel Ashkenazi and Non …
Freq6 = 0.2 | People6 = China Beijing Shijiazhuan…

Disease Associations

A*1104 is associated with increased risk for cervical neoplasia resulting from human papillomavirus infection [cite journal | author = Chan D, Cheung T, Tam A, Cheung J, Yim S, Lo K, Siu N, Zhou D, Chan P | title = Risk association between human leukocyte antigen-A allele and high-risk human papillomavirus infection for cervical neoplasia in Chinese women. | journal = J Infect Dis | volume = 192 | issue = 10 | pages = 1749–56 | year = 2005 | pmid = 16235173 | doi = 10.1086/497342]

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