HLA-A3

See also: History and naming of human leukocyte antigens

HLA-A3 (A3) is a human leukocyte antigen serotype within HLA-A serotype group. The serotype is determined by the antibody recognition of α³ subset of HLA-A α-chains. For A3, the alpha, "A", chain are encoded by the HLA-A*03 allele group and the β-chain are encoded by B2M locus.^[1] This group currently is dominated by A*03:01. A3 and A*03 are almost synonymous in meaning. A3 is more common in Europe, it is part of the longest known multigene haplotype, A3~B7~DR15~DQ6.^[2]

HLA-A3
(MHC Class I, A cell surface antigen)
HLA-A3
About
Protein	transmembrane receptor/ligand
Structure	αβ heterodimer
Subunits	HLA-A*03--, β2-microglobulin
Older names	HL-A3
Subtypes
Subtype allele Available structures A3.1 *03:01 A3.2 *03:02
Rare alleles
Subtype allele Available structures A3.5 *03:05
Alleles link-out to IMGT/HLA database at EBI

Serotype

A3 recognition of some HLA A*03 gene products^[3]

A*03	A3	Sample
allele	%	size (N)
*03:01	99	3504
*03:02	78	342
*03:05	20	5

A3 is primarily composed of A*03:01 and *03:02 which serotype well with anti-A3 antibodies. There are 26 non-synonymous variants of A*03, 4 nulls, and 22 protein variants.

Associated diseases

A3 serotype is a secondary risk factor for myasthenia gravis^[4] and lower CD8⁺ levels in hemochromatosis patients.^[5][6] The HFE (Hemochromatosis) locus lies between A3 and B7 within the A3~DQ6 superhaplotype.^[7]

In HIV

HLA-A3 selects HIV evolution for a mutation Gag KK9 epitope and results in a rapid decline in the CD8 T-cell response. CD8 T-cells are responsible for quickly killing HIV infected CD4+ cells.^[8] This type of evolved response may not be specific for HLA-A3 and since HIV is capable of adapting quickly in situ to selective factors.

Alleles

HLA A*03:01 frequencies

Study population	Freq.  (in %)[9]
Finland	25.0
India Tamil Nadu Nadar	20.5
Czech Republic	18.9
Belgium	17.1
Ireland Northern	14.3
Australia New South Wales	13.8
Georgia Svaneti Svans	13.8
Georgia Tbilisi Georgian…	13.8
Pakistan Burusho	13.0
Cape Verde Northwestern I…	12.0
Ireland South	11.6
Romanian	11.6
Croatia	11.0
USA Caucasians (3)	10.8
Italy North (1)	9.7
USA African Americans (2)	9.4
India Mumbai Marathas	9.3
India West Bhils	9.0
Portugal Centre	9.0
Pakistan Pathan	8.7
Cameroon Beti	8.6
Cameroon Bamileke	7.8
Pakistan Kalash	7.5
Saudi Arabia Guraiat and …	7.5
USA Hispanic	7.3
India North Delhi	7.2
Madeira	7.0
Russia Tuva (2)	6.9
Tunisia	6.7
USA North American Native…	6.7
Cape Verde Southeastern I…	6.5
Azores Santa Maria and Sa…	6.4
Pakistan Baloch	6.3
Guinea Bissau	6.2
Israel Arab Druse	6.0
South African Natal Zulu	6.0
USA South Texas Hispanics	6.0
India North Hindus	5.8
Zambia Lusaka	5.8
Iran Baloch	5.6
Uganda Kampala	5.5
Jordan Amman	5.2
Kenya	5.2
Brazil	5.1
Oman	5.1
Cameroon Pygmy Baka	5.0
Georgia Tbilisi Kurds	5.0
Sudanese	4.8
Bulgaria	4.6
Pakistan Brahui	4.6
China Beijing	4.5
Australia Indig. Cape Yor…	4.4
China Inner Mongolia	4.4
Mali Bandiagara	4.4
Pakistan Sindhi	4.4
China Qinghai Hui	4.1
Zimbabwe Harare Shona	4.0
Cameroon Sawa	3.8
Senegal Niokholo Mandenka	3.8
Kenya Luo	3.6
Morocco Nador Metalsa Cla…	3.4
Kenya Nandi	3.1
Mex. Guadalajara Mestizos…	3.1
China Guangzhou	2.9
China North Han	2.9
Mongolia Buriat	2.9
China Tibetans	2.5
China Yunnan Nu	2.5
Mexico Mestizos	2.4
American Samoa	2.0
Singapore Javanese Indone…	2.0
Allele frequencies presented, only

HLA A*03:02 frequencies

Study population	Freq.  (in %)[9]
Georgia Tbilisi Kurds	8.3
Morocco Nador Metalsa Cla…	4.1
Pakistan Karachi Parsi	2.8
Israel Arab Druse	2.5
India New Delhi	2.3
Sudanese	2.3
India North Delhi	2.2
India West Coast Parsis	2.0
Portugal Centre	2.0
India Andhra Pradesh Goll…	1.7
Pakistan Kalash	1.7
Pakistan Baloch	1.6
Georgia Tbilisi Georgian…	1.4
Saudi Arabia Guraiat and …	1.4
Oman	1.3
Pakistan Sindhi	1.3
India North Hindus	1.0
Pakistan Pathan	1.0
South Africa Natal Tamil	1.0
USA South Texas Hispanics	0.8
Allele frequencies presented, only

Associated diseases

A*03:01 modulates increased risk for multiple sclerosis^[10]

A3~B haplotypes

A3-B7 is part of the A3~DQ2 superhaplotype A3-B8 (Romania, svanS)
A3~B35 (Bulgaria, Croatia, E. Black Sea)
A3~B55 (E. Black Sea)

A3~Cw7~B7

A3~B7 is bimodal in frequency in Europe with one node in Ireland and the other in Switzerland, relatively speaking Switzerland appears to be higher. A3~Cw7~B7 is one of the most common multigene haplotypes in the western world, particularly in Central and Eastern Europe.

A*03:01 ~ C*07:02 ~ B*07:02 ~ DRB1*15:01 ~ DQA1*01:02 ~ DQB1*06:02