HLA-A*02

See also: History and naming of human leukocyte antigens § Genetics

HLA-A*02 (A*02) is a human leukocyte antigen serotype within the HLA-A serotype group. The serotype is determined by the antibody recognition of the α2 domain of the HLA-A α-chain. For A*02, the α chain is encoded by the HLA-A*02 gene and the β chain is encoded by the B2M locus.^[1] In 2010 the World Health Organization Naming Committee for Factors of the HLA System revised the nomenclature for HLAs. Before this revision, HLA-A*02 was also referred to as HLA-A2, HLA-A02, and HLA-A*2.^[2]

HLA-A2
(MHC Class I, A cell surface antigen)
Rendering of 2git​: α (A*02:01 gene product), β2-microglobulin, and HIV peptide.
About
Protein	transmembrane receptor/ligand
Structure	αβ heterodimer
Subunits	HLA-A*02--, β2-microglobulin
Older names	HL-A2
Subtypes
Subtype allele Available structures A2.1 *02:01 3hla​, 2gj6​, 2git​, 2clr​, 2bsv​, 2c7u​, 2bsu​, 2av1​, 2av7​, 1tvb​, 1tvh​, 1s8d​, 1s9w​, 1s9x​, 1s9y​, 1t1w​, 1t1x​, 1t1y​, 1t1z​, 1t20​, 1t21​, 1t22​, 1qse​, 1qr1​, 1qrn​, 1p7q​, 1jf1​, 1jht​, 1i1f​, 1i1y​, 1i4f​, 1i7r​, 1i7t​, 1i7u​, 1im3​, 1akj​, 1ao7​, 1b0g​, 1b0r​, 1bd2​, 1duy​, 1duz​, 1eey​, 1eez​, 1hhg​, 1hhh​, 1hhi​, 1hhj​, 1hhk​, 1hla​ A2.2F *02:02 A2.3, A203 *02:03 A2.2Y *02:05 A2.4a *02:06
Rare alleles
Subtype allele Available structures A2.4 *02:04 A2.4b *02:07 A2.5 *02:11
Alleles link-out to IMGT/HLA database at EBI

HLA-A*02 is one particular class I major histocompatibility complex (MHC) allele group at the HLA-A locus. The A*02 allele group can code for many proteins; as of December 2013 there are 456 different HLA-A*02 proteins.^[3] Serotyping can identify as far as HLA-A*02, which is typically enough to prevent transplant rejection (the original motivation for HLA identification). Genes can further be separated by genetic sequencing and analysis. HLAs can be identified with as many as nine numbers and a letter (ex. HLA-A*02:101:01:02N).^[2] HLA-A*02 is globally common, but particular variants of the allele can be separated by geographic prominence.

Serotype

The serotyping for the most abundant A*02 alleles is good. For A*02:03, A*02:06, A*02:07 serotyping is borderline useful. There is a separate serotyping for A203 and A210. As of December 2013, there are 456 alleles identified (mostly by sequence homology) as being A2, of those 27 are nulls, and a large majority have unknown serotypes, although it is highly probable that they will all return A2 serotypes.^[3]

A2 recognition of some HLA A*02 gene products^[4]

A*02	A2	Sample
allele	%	size (N)
*02:01	98	6315
*02:02	81	859
*02:03	64	472
*02:05	81	462
*02:06	68	636
*02:07	80	135
*02:11	74	228

Disease associations

HLAs serve as the primary link between the immune system and interior of cells. Thus any alteration to the HLA that induces decreased binding to a certain peptide or increased binding to a certain peptide, is expressed as, respectively, increased susceptibility to disease or decreased susceptibility to disease. In other words, certain HLAs may be incapable of binding any of the short peptides produced by proteolysis of pathogenic proteins. If HLAs bind none of the peptides produced by a pathogen, then there is no way for the immune system to tell that a cell is infected. Thus the infection can proliferate largely unchecked. It works the other way too. Some HLAs bind pathogenic peptide fragments with very high affinity. This in essence "supercharges" their immune system in regards to that particular pathogen, allowing them to easily control an infection that might otherwise be devastating.^[5]

Spontaneous abortion

The HLA-A*02 antigen has been associated with spontaneous abortion in infertile couples. In essence, there are indicators, albeit from a small study comparing HLA expression in fertile and infertile couples, that HLA-A*02 may induce increased maternal immune response to the fetus. This immune response could be compared to an allergic reaction, and, if severe enough, induces abortion of the fetus.^[6] Although this is a very interesting correlation, the study which first uncovered this link was quite small and more work needs to be done to verify this hypothesis.

Human immunodeficiency virus

HLA-A*02 appears to stimulate peripheral blood mononuclear cells in a manner that inhibits HIV replication. This could be the reason for a documented 9-fold reduced risk of HIV transmission to infants during childbirth.^[7] HIV has evolved mechanisms to combat immune recognition. HIV produces a protein called Nef that binds to the cytoplasmic tail of HLA-A and B and diverts it to the lysosomes for destruction. This prevents the HLAs from being expressed on the cell surface and then functioning properly.^[8] In addition, there are several HLA-A*02 haplotypes that appear to contribute heavily to higher or lower viral loads in HIV patients. HLA-A*02-C*16 and HLA-A*02-B*45 have been shown to contribute to significantly increased viral loads (greater than 100,000 copies per milliliter).^[9] In summation, HLA-A*02 appears to be somewhat less effective than other HLA-As at protecting against HIV infections.

Hodgkin lymphoma

HLA-A*02 has been linked with decreased risk of developing Epstein-Barr virus (EBV)-positive Hodgkin lymphoma(HL). Among patients with EBV+ HL, only 35.5% of people expressed HLA-A*02 compared to 50.9% in the EBV-HL group and 53% in the control group. This is a significant decrease and is almost certainly a result of the abnormally efficient binding of HLA-A*02 to peptides originating from EBV.^[10] This high affinity increases the probability of CD8+ t-cell recognition of EBV peptides held by HLA-A*02 complexes. This, in turn, enhances the immune system's ability to control and clear the EBV, which decreases the change of developing Hodgkin Lymphoma as a result of the infection.

By haplotype

A*02:Cw*16 is associated with increased higher viral load in HIV^[9]

Alleles

A*02:01 allele frequency

HLA A*02:01 frequencies Study population Freq.  (in %)^[11] Mexico Sonora Seri 54.5 USA Arizona Pima 43.6 USA New Mexico Canoncito ... 37.8 Finland 34.4 Mexico Mestizos 34.1 Georgia Tbilisi Georgian... 31.0 Bulgaria 30.0 Philippines Ivatan 30.0 Spain Catalonia Girona 29.9 USA South Dakota Lakota S... 29.7 Portugal North 29.3 Italy North pop 1 28.9 Mexico Zaptotec Oaxaca 28.4 Italy Bergamo 28.0 Czech Republic 27.4 Ireland Northern 27.4 USA Caucasian (2) 27.2 Spain Basque Gipuzkoa Pro... 27.0 Belgium 26.6 Croatia 26.3 Australia New South Wales 26.1 Portugal Centre 26.0 Turkey (1) 25.7 Mexico Chihuahua State Ta... 25.0 Romanian 25.0 Ireland South 24.6 Mexico Guadalajara Mestizo 22.3 China Tibet 21.8 USA North American Native... 21.7 USA South Texas Hispanics 21.7 Oman 21.6 Venezuela Perja Mountain ... 21.6 Georgia Svaneti Svans 21.3 Brazil Terena 20.8 Iran Baloch 20.2 Japan Ainu Hokkaido 20.0 Brazil 19.2 China Beijing 18.7 Uganda Kampala 18.4 Morocco Nador Berber 17.8 Australia Indig. Cape Yor... 17.5 Tunisia 17.5 Sudanese 17.3 South Korea (3) 16.5 Mongolia Buriat 14.3 Burkina Faso Rimaibe 13.8 Jordan Amman 13.4 Zambia Lusaka 12.8 USA African Americans (3) 12.1 Japan (3) 11.6 India Tamil Nadu Nadar 10.7 Japan Okinawa Ryukyuan 10.2 Zimbabwe Harare Shona 9.1 Ecuador Cayapa 9.0 Kenya 8.7 Georgia Tbilisi Kurds 8.3 Mali Bandiagara 8.3 Senegal Niokholo Mandenka 8.1 Cameroon Yaounde 7.1 Singapore Riau Malay 6.5 India North Hindus 5.8 Taiwan Hakka 5.5 Taiwan Pazeh 5.5 China South Han 5.3 Burkina Faso Fulani 5.1 Sri Lanka Colombo Sinhalese 4.9 China Guangxi Maonan 4.6 Singapore Javanese Indonesian 4.0 Taiwan Paiwan 3.9 India Andhra Pradesh Goll... 3.4 Singapore Thai 3.1 Taiwan Rukai 3.0 Taiwan Tsou 2.9 Pakistan Karachi Parsi 2.8 Taiwan Ami 2.6 South African Natal Zulu 2.5 New Caledonia 2.4 USA Alaska Yupik Natives 2.4 PNG Wanigela 2.1 Taiwan Puyuma 2.0 Taiwan Tao 2.0 India Mumbai Marathas 1.9 Thailand 1.8 South Africa Natal Tamil 1.0 Allele frequencies presented, only

A*02:02 allele frequency

HLA A*02:02 frequencies Study population Freq.  (in %)^[11] Cameroon Bamileke 10.4 Senegal Niokholo Mandenka 9.1 Cameroon Yaounde 8.2 Mali Bandiagara 7.6 Guinea Bissau 6.2 Cameroon Beti 6.0 Burkina Faso Rimaibe 5.3 Kenya 4.9 Georgia Svaneti Svans 3.8 USA African Americans (2) 3.7 Zimbabwe Harare Shona 3.6 South African Natal Zulu 3.5 Uganda Kampala 3.4 Saudi Arabia Guraiat and ... 2.4 Pakistan Brahui 2.3 Zambia Lusaka 2.3 Israel Arab Druse 2.0 Sudanese 1.8 India North Delhi 1.7 Pakistan Karachi Parsi 1.7 China Qinghai Hui 1.4 Portugal North 1.1 Georgia Tbilisi Georgian... 1.0 Tunisia 1.0 Allele frequencies presented, only

A*02:03 allele frequency

HLA A*02:03 frequencies Study population Freq.  (in %)^[11] China Guangxi Maonan 17.6 China Yunnan Lisu 15.2 Thailand Northeast 12.2 China South Han 10.8 China Guangzhou 9.8 Singapore Javanese Indonesian 9.0 China Yunnan Nu 8.2 Thailand 7.7 Taiwan Minnan pop 1 6.4 Taiwan Puyuma 6.0 Taiwan Siraya 5.9 Singapore Riau Malay 5.2 India Khandesh Pawra 5.0 India West Bhils 5.0 Taiwan Pazeh 4.5 USA Asian 4.2 India Mumbai Marathas 3.7 Taiwan Hakka 3.6 China North Han 2.4 Sri Lanka Colombo Sinhalese 2.4 China Qinghai Hui 2.3 Burkina Faso Rimaibe 1.1 Taiwan Saisiat 1.0 Allele frequencies presented, only

A*02:05 allele frequency

HLA A*02:05 frequencies Study population Freq.  (in %)^[11] Burkina Faso Fulani 9.2 Kenya Nandi 8.7 Sudanese 6.5 Saudi Arabia Guraiat and ... 6.1 Italy North (1) 5.8 South African Natal Zulu 5.5 Cameroon Pygmy Baka 5.0 Georgia Tbilisi Kurds 5.0 Burkina Faso Rimaibe 4.3 Israel Arab Druse 4.0 Cameroon Sawa 3.8 Turkey (1) 3.5 Mongolia Buriat 3.2 Zimbabwe Harare Shona 3.1 India New Delhi 3.0 USA African America 3.0 Bulgaria 2.7 Cameroon Bamileke 2.6 Kenya Luo 2.6 Pakistan Sindhi 2.5 Tunisia 2.5 Cuban Mulatto 2.4 Czech Republic 2.4 Spain Catalonia Girona 2.3 Cameroon Yaounde 2.2 Mali Bandiagara 2.2 Uganda Kampala 2.2 Italy Bergamo 2.1 Oman 2.1 USA African Americans (2) 1.7 China North Han 1.4 Georgia Tbilisi Georgian... 1.4 Kenya 1.4 Ireland Northern 1.2 Cameroon Beti 1.1 India North Delhi 1.1 Senegal Niokholo Mandenka 1.1 USA Caucasians (3) 1.1 India North Hindus 1.0 Mexico Mixtec Oaxaca 1.0 Portugal Centre 1.0 Spain Basque Gipuzkoa Pro... 1.0 Allele frequencies presented, only

A*02:06 allele frequency

HLA A*02:06 frequencies Study population Freq.  (in %)^[11] Mexico Mixe Oaxaca 34.9 Mexico Zaptotec Oaxaca 26.1 Mexico Mixtec Oaxaca 21.6 Pakistan Kalash 21.6 Japan Ainu Hokkaido 20.0 Japan Okinawa Ryukyuan 18.3 USA Alaska Yupik Natives 16.5 USA Hawaii Okinawa 14.3 American Samoa 13.0 Mexico Chihuahua State Ta... 12.5 Taiwan Puyuma 12.0 USA South Dakota Lakota S... 10.5 Taiwan Atayal 9.4 Japan pop3 8.7 Japan pop5 8.4 India North Delhi 7.7 Japan Central 7.7 USA Arizona Pima 7.6 Taiwan Bunun 7.4 USA South Texas Hispanics 7.3 USA North American Native... 7.2 China North Han 7.1 South Korea pop 3 7.1 Russia Tuva pop 2 6.9 Mexico Mestizos 6.1 Pakistan Burusho 6.0 Taiwan Taroko 5.5 Singapore Chinese Han 5.2 USA Asian 5.0 USA New Mexico Canoncito ... 4.9 China Beijing 4.8 China Beijing Shijiazhuan... 4.7 Hong Kong Chinese 4.7 China Guangxi Maonan 4.6 Mongolia Buriat 4.3 China Guangzhou 4.0 Philippines Ivatan 4.0 Singapore Chinese 4.0 Taiwan Pazeh 3.6 China South Han 3.5 Taiwan Thao 3.3 Pakistan Sindhi 3.2 USA Hispanic 3.2 Pakistan Pathan 3.1 India New Delhi 3.0 Taiwan Rukai 3.0 India North Hindus 2.9 Taiwan Minnan pop 1 2.9 Taiwan Paiwan 2.9 India Andhra Pradesh Goll... 2.8 Taiwan Hakka 2.7 Papua New Guinea Eastern ... 2.6 Thailand 2.5 Sri Lanka Colombo Sinhalese 2.4 Pakistan Brahui 2.3 Papua New Guinea Wanigela 2.1 Singapore Javanese Indone... 2.0 Singapore Riau Malay 2.0 Singapore Thai 2.0 Taiwan Saisiat 2.0 Taiwan Siraya 2.0 Pakistan Baloch 1.6 Taiwan Ami 1.5 Zambia Lusaka 1.2 Iran Baloch 1.1 Pakistan Karachi Parsi 1.1 Allele frequencies presented, only

A*02:07 allele frequency

HLA A*02:07 frequencies Study population Freq.  (in %)^[11] Thailand Northeast 15.7 China Guangxi Maonan 13.4 Hong Kong Chinese 13.1 Singapore Chinese 13.1 Singapore Thai 12.2 Singapore Chinese Han 11.6 Taiwan Minnan pop 1 11.3 Thailand 10.9 China South Han 9.4 China Guangzhou 9.3 China Yunnan Nu 8.2 Taiwan Hakka 8.2 Taiwan Siraya 6.9 China Beijing 6.7 USA Asian 6.6 Taiwan Pazeh 6.4 China North Han 4.3 China Qinghai Hui 3.6 Japan (3) 3.4 South Korea (3) 3.0 China Inner Mongolia 2.5 China Yunnan Lisu 2.2 Mongolia Buriat 2.1 Singapore Riau Malay 2.0 Taiwan Thao 1.7 China Tibet Autonomous Region 1.6 Russia Tuva pop 2 1.6 USA Hawaii Okinawa 1.4 Burkina Faso Fulani 1.0 Japan Ainu Hokkaido 1.0 Singapore Javanese Indonesian 1.0 Allele frequencies presented, only

A*02:11 allele frequency

HLA A*0211 frequencies Study population Freq.  (in %)^[11] India Khandesh Pawra 16.0 South Africa Natal Tamil 13.0 India Andhra Pradesh Goll... 9.7 India Mumbai Marathas 8.6 Sri Lanka Colombo Sinhale... 7.4 India North Hindus 6.7 Ecuador Cayapa 4.8 India West Bhils 4.0 Pakistan Sindhi 2.5 Pakistan Brahui 2.3 Pakistan Pathan 2.0 Singapore Javanese Indonesian 2.0 India North Delhi 1.7 Pakistan Baloch 1.6 Singapore Riau Malay 1.2 Iran Baloch 1.1 Pakistan Burusho 1.1 Allele frequencies presented, only

A2-B haplotypes

A2-B7 (Node in Netherlands) A2-B5

• A2-B51
• A2-B52

A2-B8
A2-B13
A2-B14

• A2-B64
• A2-B65

A2-B15

• A2-B62
• A2-B63
• A2-B70,71,75,76
• A2-B46 (Node in Southern China, may be most abundant haplotype)

A2-B16

• A2-B44
• A2-B45

A2-B18
A2-B27
A2-B35
A2-B37 A2-B39 (Node in North American Amerinds)
A2-B40

• A2-B60
• A2-B61

A2-B46

A2-Cw5-B44

HLA A2-B44 haplotype frequencies

		freq		Rank in
ref.	Population	(%)		Pop.
^[12]	Cornish	11.4	^1	1
^[13]	Ireland	9.2		2
^[14]	Northern Ireland	8.0	^1	2
^[12]	Sweden	7.2		2
^[15]	Swiss	6.9		2
^[12]	Polish	6.2		1
^[12]	Spanish	5.9		1
^[12]	Ukraine	5.9		1
^[16]	Dutch Netherlands	5.9		3
^[12]	Dane	4.8		1
^[12]	Czech	4.7		3
^[12]	Basque	4.7		3
^[12]	Greek	4.5		3
^[12]	Yugoslavian	4.4
^[12]	Hungarian	3.5
^[12]	British	2.6		4
	Romania	2.5
^[12]	Austria	2.4
^1Cw*0501 (Eur.)

A2-Cw5-B44 is the multi-serotype designation for the haplotype HLA-A*02:01~C*05:01~B*4402, the class I portion, of an ancestral haplotype (A2~B44~DR4~DQ8). The full haplotype is (for relative distances) see Human leukocyte antigens:

A*02:01 ~ C*05:01 ~ B*44:02 ~ DRB1*04:01 ~ DQA1*03:01 ~ DQB1*03:02

Another haplotype that is more common in Central Europe is the (A2-B44-DR7-DQ2)

A*02:01 ~ C*05:01 ~ B*44:02 ~ DRB1*07:01 ~ DQA1*02:01 ~ DQB1*02:02

Over northwestern Europe A2-B44 shows a single common ancestor which contributed the Cw5 allele to the haplotype. The haplotype appears to have been introduced early in European prehistoric period, frequencies of the haplotype generally correlate with A1-Cw7-B8 and A2-B7. The haplotype is considerably more equilibrated relative to A1-B8 and a possible reason is gene flow from iberia or the east with related haplotypes after initial migrations.

References

1. Arce-Gomez B, Jones EA, Barnstable CJ, Solomon E, Bodmer WF (Feb 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. "HLA Nomenclature @ hla.alleles.org". Anthony Nolan Research Institute. 10 Nov 2013. Retrieved 8 Dec 2013.
3. "Allele Search Tool". European Molecular Biology Laboratory. 2013. Retrieved 20 December 2013.
4. Allele Query Form IMGT/HLA - European Bioinformatics Institute
5. Daniel M. Davis (2014). The Compatibility Gene. How Our Bodies Fight Disease, Attract Others, and Define Our Selves. Oxford: Oxford University Press. ISBN 978-0-19-931641-0.
6. Komlos L, Klein T, Korostishevsky M (Aug 2007). "HLA-A2 class I antigens in couples with recurrent spontaneous abortions". International Journal of Immunogenetics. 34 (4): 241–6. doi:10.1111/j.1744-313X.2007.00682.x. PMID 17627758. S2CID 12367668.
7. Grene E, Pinto LA, Cohen SS, Trivett MT, Simonis TB, Liewehr DJ, Steinberg SM, Shearer GM (Feb 2001). "Generation of alloantigen-stimulated anti-human immunodeficiency virus activity is associated with HLA-A*02 expression". The Journal of Infectious Diseases. 183 (3): 409–16. doi:10.1086/318085. PMID 11133372.
8. Mann JK, Byakwaga H, Kuang XT, Le AQ, Brumme CJ, Mwimanzi P, Omarjee S, Martin E, Lee GQ, Baraki B, Danroth R, McCloskey R, Muzoora C, Bangsberg DR, Hunt PW, Goulder PJ, Walker BD, Harrigan PR, Martin JN, Ndung'u T, Brockman MA, Brumme ZL (16 September 2013). "Ability of HIV-1 Nef to downregulate CD4 and HLA class I differs among viral subtypes". Retrovirology. 10 (1): 100. doi:10.1186/1742-4690-10-100. PMC 3849644. PMID 24041011.
9. Tang J, Tang S, Lobashevsky E, Myracle AD, Fideli U, Aldrovandi G, Allen S, Musonda R, Kaslow RA (Aug 2002). "Favorable and unfavorable HLA class I alleles and haplotypes in Zambians predominantly infected with clade C human immunodeficiency virus type 1". Journal of Virology. 76 (16): 8276–84. doi:10.1128/JVI.76.16.8276-8284.2002. PMC 155130. PMID 12134033.
10. Niens M, Jarrett RF, Hepkema B, Nolte IM, Diepstra A, Platteel M, Kouprie N, Delury CP, Gallagher A, Visser L, Poppema S, te Meerman GJ, van den Berg A (Nov 2007). "HLA-A*02 is associated with a reduced risk and HLA-A*01 with an increased risk of developing EBV+ Hodgkin lymphoma" (PDF). Blood. 110 (9): 3310–5. doi:10.1182/blood-2007-05-086934. PMID 17630352. S2CID 24567105.
11. 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.
12. Sasazuki, Takehiko; Tsuji, Kimiyoshi; Aizawa, Miki (1992). HLA 1991: proceedings of the eleventh International Histocompatibility Workshop and Conference, held in Yokohama, Japan, 6-13 November, 1991. Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-262390-7.
13. Finch T, Lawlor E, Borton M, Barnes CA, McNamara S, O'Riordan J, McCann SR, Darke C (1997). "Distribution of HLA-A, B and DR genes and haplotypes in the Irish population". Experimental and Clinical Immunogenetics. 14 (4): 250–63. PMID 9523161.
14. Middleton D, Williams F, Hamill MA, Meenagh A (Dec 2000). "Frequency of HLA-B alleles in a Caucasoid population determined by a two-stage PCR-SSOP typing strategy". Human Immunology. 61 (12): 1285–97. doi:10.1016/S0198-8859(00)00186-5. PMID 11163085.
15. Grundschober C, Sanchez-Mazas A, Excoffier L, Langaney A, Jeannet M, Tiercy JM (Jun 1994). "HLA-DPB1 DNA polymorphism in the Swiss population: linkage disequilibrium with other HLA loci and population genetic affinities". European Journal of Immunogenetics. 21 (3): 143–57. doi:10.1111/j.1744-313X.1994.tb00186.x. PMID 9098428. S2CID 29932752.
16. Schipper RF, Schreuder GM, D'Amaro J, Oudshoorn M (Nov 1996). "HLA gene and haplotype frequencies in Dutch blood donors". Tissue Antigens. 48 (5): 562–74. doi:10.1111/j.1399-0039.1996.tb02670.x. PMID 8988539.