HLA-A

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HLA-A2 with bound peptide
major histocompatibility complex, class I, A
Identifiers
Symbol(s) HLA-A
Entrez 3105
OMIM 142800
RefSeq NM_002116
UniProt P30443
Other data
Locus Chr. 6 p21.31

HLA-A belongs to the MHC (human leukocyte antigen= HLA) class I heavy chain receptors. The HLA-A is a heterodimeric receptor consisting of a HLA-A mature gene product and β2-microglobulin. The mature A chain is anchored in the membrane. MHC Class I molecules, like HLA-A, are expressed in nearly all cells, and present small peptides to the immune system which surveys for non-self peptides.

HLA-A is a locus on chromosome 6 that encodes for a large number of HLA-A alleles that are Class-I MHC receptors. HLA is located on the distal end of the HLA region.

Contents

[edit] Function

MHC Class I molecules present smaller peptides, generally 9mers but longer molecules are tolerated, to the immune system. Several target cells include CD8+ T-lymphocytes. In response to signalling these lymphocytes result in apototic cell death. This mechanism is the result of responses to viral infection or intracellular microbial infections in which, as a means of preventing propogation, affected cells are killed and the antigens are presented to the immune system for Class II presentation and antibody development. Over a short period of time antibodies develop that can neutralize the ability of viruses and invasive bacteria to invade cells.

[edit] Structure

The HLA-A chain forms a binding cleft much like the MHC Class II molecules, the sides of the cleft are composed of alpha helices, the base is beta sheet and one end the relative closure limits the optimal length of peptide.

[edit] Associated Diseases

[edit] By Sertoype

A3 Serotype: Secondary risk factor for myasthenia gravis[1], lower CD8+ levels in hemochromatosis patients[2][3]

A24 Serotype: Secondary risk factor for myasthenia gravis[1], Buerger's_disease[4]

A26 Serotype: Adult T-cell Leukemia, Japan [5][6]

[edit] By Allele

A*0101: Alters Type 1 diabetes risk [7]

A*0301: Modulates increased risk for Multiple Sclerosis[8]

A*1104: Increased risk for cervical neoplasia resulting from human papillomavirus infection [9]

A*2402: Ankylosing spondylitis, secondary risk factor[10], alters type 1 diabetes risk [7][11], and allele associated with thyomoma induced myasthenia gravis.

A*3002: Alters Type 1 diabetes risk [7]

A*68 : higher viral load in HIV[12]

[edit] By Haplotype

A*02:Cw*16 : higher viral load in HIV[12]
A*23:B*14 : higher viral load in HIV[12]
A*23:Cw*07 : higher viral load in HIV[12]
A*30:Cw*03 : higher viral load in HIV[12]

[edit] Nomenclature

HLA alleles[13] and specificity
. Some Allele groups have been updated with recent information from the IMGT/HLA Database

Explanation - within each allele group there are alleles that are recognized by the serological typing for that group(e.g. A24-serotype) some within the group may also recognize the broad antigen typing (A9, A10, A19, A28) or only the broad antigen typing, some by alternative serological within the group (e.g. A2403), and some by no serological method. Obviously some groups are more closely related than other groups, and this is often reflected in broad antigen reactivity.


A*01

  • 24 alleles: 21 non-synonomous variants, 7 Nulls, 14 protein variants
  • A1-Serotype: A*0101, *0102, *0103, *0107, *0106 and *0108
  • A* Serotype unknown: A*0109, *0110, *0112, *0113, *0114, *0117, *0119, *0120
  • Null: A*0104N, *0105N, *0111N, *0115N, *0116N, *0118N


A*02

  • 122 alleles: 103 non-synonomous variants, 8 nulls, 95 protein variants.
  • A2-Serotype: A*0201, *0201L, *0202 to *0209, *0211 to *0214, *0216 to *0218, *0222 to *0225, *0229, *0231, *0234 to *0235, *0241 to *0242, *0246, *0250, *0259, *0266 to *0268, and *0270 to *0274
  • A203-Serotype: A*0203 (also types with A2)
  • A210-Serotype: A*0210 (also types with A2)
  • Serotype unknown: *0219, *0226, *0228, *0230, *0233, *0236 to *0240, A*0244, A*0245, A*0247 to *0249, *0251 to *0252, *0254 to *0258, *0260 to *0265, *0269, *0275 to *0281, *0284 to *0287, *0289 to *0293, *0295 to *0297, *0299, and *9201 to *9204
  • Nulls: A*0215N,*0232N,*0243N, *0253N, *0282N, *0283N, *0288N, *0294N


A*03

  • 31 alleles: 26 non-synonomous variants, 4 nulls, 22 protein variants
  • A3-Serotype: A*0301, *0302, *0304, *0307, *0308, *0309
  • Serotype unknown: A*0306, and A*0312 to A*0320, *0322 to *0325
  • only A3&Other MoAb reactive:A*305, *310
  • Null: *03010102N, *0303N, *0311N, and *0321


A*11

  • A11-Serotype: A*1101 to A*1105, A*1107, A*1108, A*1110, A*1112, A*1112 to A*1115, A*1119
  • A*1106, A*1109, A*1111, A*1116 to A*1118, A*1120
  • Nulls: A*1121N


A*23

  • A23(A9)-Serotype: A*2301, A*2304
  • A*2302, *2303, *2305, *2306, *2309, *2310, *2312
  • Null: A*2307N, *2308N, *2312N


A*24

  • A24(A9)-Serotype: A*2402, *2404, *2405 to *2406 to *2408, *2413, *2414, *2417, *2420, *2421, *2423, *2427, *2437, *2443,
  • A2403-Serotype: A*2403, 2410, *2433
  • A9-Serotype: A*2422
  • A*24 *2405, *2415, *2418, *2424 to *2426, *2417 to *2432, *2434, *2435, *2438, *2439, *2444, *2446, *2447
  • Null: A*2409N, *2411N, *2436N, *2440N, *2445N, *2448N


A*25

  • A25(A10)-Serotye: A*2501 and *2502
  • A*2503 and A*2504


A*26

  • A26(A10)-Serotype: A*2601 to *2609
  • A10-Serotype: A*2610 and *2615
  • A*2612 to A*2614
  • Null: A*2611N


A*34

  • A34(A10)-Serotype: A*3401, A*3402, and A*3404
  • A*3403, A*3405, and A*3406


  • A19
    • A29
    • A30
    • A31
    • A32
    • A33
    • A74
  • A28
    • A68
    • A69
  • A36

[edit] A Haplotypes

[edit] A1

HLA A1-B8 haplotype frequencies
[14] Ireland 14.4 1
[15] Slovak 11.9 1
[16] Northern Ireland 11.5 1 1
[15] Swedish 11.5 1
[17] Dutch Netherlands 9.8
[15] Yugoslavian 9.7 1
[15] British 9.7 1
[15] Hungarian 9.4 1
[18] CEPH France 8.5 1 1
[19] German 8.3 1
[15] Czech 7.8 1
[20] Swiss 6.7 3
[15] Belgium 5.5 2
[15] Austria 4.5 2
[21] Tuscan Italy 4.3
[15] Ukraine 4.3 3
[15] Italy 4.2 1
[15] Basque 4.2
[15] Portuguese 4.2 2
[15] Polish 4.0
[22] Uganda 3.7 1
[15] Uralic 3.1 3
[15] Spanish 2.8 4
[1] Romania 2.8
[15] Albania 2.5
[15] Greek 2.3
[2] Northern Greece 2.1
[23] Crete 1.9
[22] Luo Kenya 1.7 2
[22] Nandi Kenya 1.4 2
[24] Oman Arabia 1.4
[15] Japanese 0.1
1Cw*0701 (Eur.), 2Cw*0704 (Afr.)
HLA A1-B57 haplotype frequencies
[15] Iyers India 4.8
[15] Buriat 2.8
[15] Austrian 2.7
[15] Cornish 2.7
[15] Basque 2.5
[15] Yakut 2.5
[15] Kazakh 2.3
[15] Vietname 2.0
[15] N. Han 1.7
[15] Thais 1.0
[15] Basque 0.7
    • A1-B7 Armenia, Austria, NW Europe(regional recombinant between A1-B8 and A2/A3-B7)
    • A1-B8
      • Node- Western Ireland
      • Diversity - East and NorthWestern Africa
      • Cw Linkage - Cw7, Europe Cw*0701, Africa Cw*0701, Cw*0704
      • DR Linkage - DR3, NW Europe DRB1*0301, SE Europe DRB1*0301/*0302
      • DQ Linkage - DQ2, NW Europe DQA1*0501:DQB1*0201
      • Linkage disequilbrium - Europe, high; NW Europe amoung the highest.
      • "Super B8 Haplotype","Ancestral Haplotype": A1-B8-DR3-DQ2
      • Reported as under positive selection in Europe's recent past
    • A1-B13 Uralic
    • A1-B35 (Albania, Belgium, Italy, Greece, France - Eastern mediterranian in origin)

HLA A1-B58 haplotype frequencies
[15] Khoi (S. Africa) 5.5 4
[15] German 2.8
[15] Swedish 2.7
[15] Basque 2.5
[15] Yakut 2.5
[15] Timor 1.8
[15] French 0.8
    • A1-B37 Yakuts, Tribal-India, Iyers-India, Mongolian, Indian, Orochon, Romanian, Yugoslavia, Korean, Albania, French, German, Manchu)
    • A1-B51 Yugoslavia, Germany, Iberia, Italy
    • A1-B52 Bharghavas-India, Tribal-India, Italy, Iberia, France
    • A1-B57 (A1-B17)
    • A1-B58 (A1-B17 where B58 is dominant): antineutrophil cytoplasmic antibodies (ANCA)[25]

[edit] A2

    • A2-B7 (Node in Netherlands)
    • A2-B8
    • A2-B13
    • A2-B14
      • A2-B64
      • A2-B65
    • A2-B15
      • A2-B62
      • A2-B63
      • A2-B70,71,75,76
    • A2-B18
    • A2-B27
    • A2-B35
    • A2-B37
    • A2-B39 (Node in North American Amerinds)
    • A2-B40
      • A2-B60
      • A2-B61
    • A2-B44
    • A2-B46 (Node in Southern China, may be most abundant haplotype)
    • A2-B51
    • A2-B52

[edit] A3

HLA A3-B7 haplotype frequencies
[26] Swiss 9.1 1
[27] Ireland 8.6
[15] Austria 7.4 1
[28] Northern Ireland 6.5 1
[29] Netherlands 6.6
[15] Belgium 6.0 1
[15] Swedish 5.7 3
[30] German 5.7
[15] Polish 4.9
[15] Romanian 3.8
[15] Armenia 3.7
[15] Portuguese 3.4
[15] British 3.4
[15] Czech 3.1
[31] Svans 2.7
[15] Albania 2.7
[32] Tuscan Italy 2.7
[15] Spanish 2.6
[15] Basque 2.5
[15] Italy 1.6
[15] Greek 1.3
[33] Bulgaria 1.1
1 Cw*0702 (Europe)
    • A3-B7 (Node in Western Ireland)
      • Cw Linkage: Cw*0702
      • DR Linkage: DRB1*1501
      • DQ Linkage: DQ6, DQA1*0102:DQB1*0602
      • A*0301:Cw*0702:B*0702:DRB1*1501:DQA1*0102:DQB1*0602
      • Haplotype of Western Eurasian origin
      • Center of diversity in western asia/middle east.
    • A3-B8 (romania, svanS)
    • A3-B35 (bulgaria, croatia, E. Black Sea)
    • A3-B55 (E. Black Sea)

[edit] A24

    • A24-B35 (Near East, Mediterranean)

[edit] A29

    • A29-Cw16-B44 (West Africa, Western Europe)

[edit] A31

    • A31-B51 (Eastern Asia, Native Americans)

[edit] A33

    • A33-B58
    • A33-B44 (Korea, Iyers, parts of asia)

[edit] References

  1. ^ a b Machens A, Löliger C, Pichlmeier U, Emskötter T, Busch C, Izbicki J (1999). "Correlation of thymic pathology with HLA in myasthenia gravis.". Clin Immunol 91 (3): 296-301. PMID 10370374.
  2. ^ 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. PMID 15607698.
  3. ^ 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. PMID 16509978.
  4. ^ Numano F, Sasazuki T, Koyama T, Shimokado K, Takeda Y, Nishimura Y, Mutoh M (1986). "HLA in Buerger's disease.". Exp Clin Immunogenet 3 (4): 195-200. PMID 3274054.
  5. ^ Nomura K, Utsunomiya A, Furushou H, Tara M, Hazeki M, Tokunaga M, Uozumi K, Hanada S, Yashiki S, Tajima K, Sonoda S (2006). "A family predisposition to adult T-cell leukemia.". J Clin Exp Hematop 46 (2): 67-71. PMID 17142956.
  6. ^ Yashiki S, Fujiyoshi T, Arima N, Osame M, Yoshinaga M, Nagata Y, Tara M, Nomura K, Utsunomiya A, Hanada S, Tajima K, Sonoda S (2001). "HLA-A*26, HLA-B*4002, HLA-B*4006, and HLA-B*4801 alleles predispose to adult T cell leukemia: the limited recognition of HTLV type 1 tax peptide anchor motifs and epitopes to generate anti-HTLV type 1 tax CD8(+) cytotoxic T lymphocytes.". AIDS Res Hum Retroviruses 17 (11): 1047-61. PMID 11485622.
  7. ^ a b c Noble J, Valdes A, Bugawan T, Apple R, Thomson G, Erlich H (2002). "The HLA class I A locus affects susceptibility to type 1 diabetes.". Hum Immunol 63 (8): 657-64. PMID 12121673.
  8. ^ 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. PMID 10746785.
  9. ^ 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. PMID 16235173.
  10. ^ de Juan M, Reta A, Belzunegui J, Figueroa M, Maruri N, Cuadrado E (2004). "HLA-A*2402 and a microsatellite (D6S248) are secondary independent susceptibility markers to ankylosing spondylitis in Basque patients.". Hum Immunol 65 (2): 175-80. PMID 14969772.
  11. ^ Nakanishi K, Inoko H (2006). "Combination of HLA-A24, -DQA1*03, and -DR9 Contributes to Acute-Onset and Early Complete {beta}-Cell Destruction in Type 1 Diabetes: Longitudinal Study of Residual {beta}-Cell Function.". Diabetes 55 (6): 1862-8. PMID 16731854.
  12. ^ a b c d e Tang J, Tang S, Lobashevsky E, Myracle A, Fideli U, Aldrovandi G, Allen S, Musonda R, Kaslow R (2002). "Favorable and unfavorable HLA class I alleles and haplotypes in Zambians predominantly infected with clade C human immunodeficiency virus type 1.". J Virol 76 (16): 8276-84. PMID 12134033.
  13. ^ Marsh SG, Albert ED, Bodmer WF, Bontrop RE, Dupont B, Erlich HA, Geraghty DE, Hansen JA, Hurley CK, Mach B, Mayr WR, Parham P, Petersdorf EW, Sasazuki T, Schreuder GM, Strominger JL, Svejgaard A, Terasaki PI, and Trowsdale J. (2005). "Nomenclature for factors of the HLA System, 2004.". Tissue antigens 65: 301-369. PMID 15787720.
  14. ^ Finch T, Lawlor E, Borton M, Barnes C, McNamara S, O'Riordan J, McCann S, Darke C (1997). "Distribution of HLA-A, B and DR genes and haplotypes in the Irish population.". Exp Clin Immunogenet 14 (4): 250-63. PMID 9523161.
  15. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at au av aw ax
  16. ^ Middleton D, Williams F, Hamill M, Meenagh A (2000). "Frequency of HLA-B alleles in a Caucasoid population determined by a two-stage PCR-SSOP typing strategy.". Hum Immunol 61 (12): 1285-97. PMID 11163085.
  17. ^ Schipper R, Schreuder G, D'Amaro J, Oudshoorn M (1996). "HLA gene and haplotype frequencies in Dutch blood donors.". Tissue Antigens 48 (5): 562-74. PMID 8988539.
  18. ^ Bugawan T, Klitz W, Blair A, Erlich H (2000). "High-resolution HLA class I typing in the CEPH families: analysis of linkage disequilibrium among HLA loci.". Tissue Antigens 56 (5): 392-404. PMID 11144287.
  19. ^ <Müller C, Ehninger G, Goldmann S (2003). "Gene and haplotype frequencies for the loci hLA-A, hLA-B, and hLA-DR based on over 13,000 german blood donors.". Hum Immunol 64 (1): 137-51. PMID 12507825.
  20. ^ Grundschober C, Sanchez-Mazas A, Excoffier L, Langaney A, Jeannet M, Tiercy J (1994). "HLA-DPB1 DNA polymorphism in the Swiss population: linkage disequilibrium with other HLA loci and population genetic affinities.". Eur J Immunogenet 21 (3): 143-57. PMID 9098428.
  21. ^ Marroni F, Curcio M, Fornaciari S, Lapi S, Mariotti M, Scatena F, Presciuttini S (2004). "Microgeographic variation of HLA-A, -B, and -DR haplotype frequencies in Tuscany, Italy: implications for recruitment of bone marrow donors.". Tissue Antigens 64 (4): 478-85. PMID 15361126.
  22. ^ a b c Cao K, Moormann A, Lyke K, Masaberg C, Sumba O, Doumbo O, Koech D, Lancaster A, Nelson M, Meyer D, Single R, Hartzman R, Plowe C, Kazura J, Mann D, Sztein M, Thomson G, Fernández-Viña M (2004). "Differentiation between African populations is evidenced by the diversity of alleles and haplotypes of HLA class I loci.". Tissue Antigens 63 (4): 293-325. PMID 15009803.
  23. ^ Arnaiz-Villena A, Iliakis P, González-Hevilla M, Longás J, Gómez-Casado E, Sfyridaki K, Trapaga J, Silvera-Redondo C, Matsouka C, Martínez-Laso J (1999). "The origin of Cretan populations as determined by characterization of HLA alleles.". Tissue Antigens 53 (3): 213-26. PMID 10203014.
  24. ^ Williams F, Meenagh A, Darke C, Acosta A, Daar A, Gorodezky C, Hammond M, Nascimento E, Middleton D (2001). "Analysis of the distribution of HLA-B alleles in populations from five continents.". Hum Immunol 62 (6): 645-50. PMID 11390040.
  25. ^ Shankarkumar U, Ghosh K, Pradhan V, Badakere S, Mohanty D (2005). "Immunogenetic association in patients with antineutrophil cytoplasmic antibodies (ANCA) from Mumbai, Maharashtra, India.". J Autoimmun 24 (3): 227-33. PMID 15848045.
  26. ^ Grundschober C, Sanchez-Mazas A, Excoffier L, Langaney A, Jeannet M, Tiercy J (1994). "HLA-DPB1 DNA polymorphism in the Swiss population: linkage disequilibrium with other HLA loci and population genetic affinities.". Eur J Immunogenet 21 (3): 143-57. PMID 9098428.
  27. ^ Finch T, Lawlor E, Borton M, Barnes C, McNamara S, O'Riordan J, McCann S, Darke C (1997). "Distribution of HLA-A, B and DR genes and haplotypes in the Irish population.". Exp Clin Immunogenet 14 (4): 250-63. PMID 9523161.
  28. ^ Middleton D, Williams F, Hamill M, Meenagh A (2000). "Frequency of HLA-B alleles in a Caucasoid population determined by a two-stage PCR-SSOP typing strategy.". Hum Immunol 61 (12): 1285-97. PMID 11163085.
  29. ^ Schipper R, Schreuder G, D'Amaro J, Oudshoorn M (1996). "HLA gene and haplotype frequencies in Dutch blood donors.". Tissue Antigens 48 (5): 562-74. PMID 8988539.
  30. ^ <Müller C, Ehninger G, Goldmann S (2003). "Gene and haplotype frequencies for the loci hLA-A, hLA-B, and hLA-DR based on over 13,000 german blood donors.". Hum Immunol 64 (1): 137-51. PMID 12507825.
  31. ^ Sánchez-Velasco P, Leyva-Cobián F (2001). "The HLA class I and class II allele frequencies studied at the DNA level in the Svanetian population (Upper Caucasus) and their relationships to Western European populations.". Tissue Antigens 58 (4): 223-33. PMID 11782273.
  32. ^ Marroni F, Curcio M, Fornaciari S, Lapi S, Mariotti M, Scatena F, Presciuttini S (2004). "Microgeographic variation of HLA-A, -B, and -DR haplotype frequencies in Tuscany, Italy: implications for recruitment of bone marrow donors.". Tissue Antigens 64 (4): 478-85. PMID 15361126.
  33. ^ Ivanova M, Rozemuller E, Tyufekchiev N, Michailova A, Tilanus M, Naumova E (2002). "HLA polymorphism in Bulgarians defined by high-resolution typing methods in comparison with other populations.". Tissue Antigens 60 (6): 496-504. PMID 12542743.

[edit] links

Molecular Anthropology Yahoo Group
HLA Allele and Haplotype Frequency Database

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