HLA-A11 explained

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 homologue HLA-A11 'alpha chain' (Cyan), β2-microglobulin (Rose), HBV peptide (yellow).
Protein Type:transmembrane receptor/ligand
Structure:αβ heterodimer
Subunit Genes:HLA-A
Alias:HL-A11
Linkout:HAwA
Isoformcount:2
Subunit1:allele
Nick1:A11E, A11.1
Allele1a:1101
Images1:,,,
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 allele group and the β-chain are encoded by B2M locus.[1] This group currently is dominated by A*1101. A11 and A 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]

Serotype

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,[3] [4] pulmonary tuberculosis,[5] leprosy,[6] and cytomegalovirus infection with epilepsy.[7] 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.[8] In osteosarcoma A11 was found elevated.[9]

There is a strong association between anti-depressant induced hepatitis and HLA-A11.[10] In autoimmune hepatitis, A11 has a synergistic effect, acting together with DR4 and DR3 to increase the odds of disease to over 300.[11]

A11 is also part of a haplotype A11-Cw4-B35-DR1-DQ1 that is a second factor in the rapid progression of HIV.[12] 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.[13]

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.[14] [15]

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,[16] [17] More recent studies show A11 is down-regulated, and that other genetic defects are a likely cause.[18] The ability to present EB virus antigens revealed a defect in the process after antigen process but before TAP1 involvement.[19] Other studies indicated that peptides bind A11 in delivery to the cell surface for CTL screening, but fall off, and are destroyed intracellularly.[20] 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

Disease associations

A*1104 is associated with increased risk for cervical neoplasia resulting from human papillomavirus infection[21]

A11-B haplotypes

A11-B13

Notes and References

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

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