Major histocompatibility complex, class II, DQ alpha 1 explained

Major histocompatibility complex, class II, DQ alpha 1, also known as HLA-DQA1, is a human gene present on short arm of chromosome 6 (6p21.3) and also denotes the genetic locus which contains this gene.^[1] The protein encoded by this gene is one of two proteins that are required to form the DQ heterodimer, a cell surface receptor essential to the function of the immune system.

Function

HLA-DQA1 belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen-presenting cells (APC: B lymphocytes, dendritic cells, macrophages).^[1]

Gene structure and polymorphisms

The alpha chain contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular protein domains, exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation.^{[1] [2]}

Alleles

DQ1

There are four commonly encountered DQA1 alleles: DQA1*0101, *0102, *0103, *0104. These alleles are always found in haplotypes with HLA-DQB1*05 (DQ5) and HLA-DQB1*06 (DQ6). DQ1 is a serotype, rare among serotypes for human class II antigens, in that the antibodies to DQ1 react to the alpha chain of HLA DQ, these DQA1 allele gene products.

DQA1	linked DQB1 allele
Rowspan = 6		0101	0501	0301
0102	0502		0602	0604		0609
0103	0501	0502	0601	0602	0603
0104	0501	0503	0602
0105	rare
0106	rare
See haplotype table in HLA-DQ. Unbolded are rare haplotypes
Link to haplotypes can be followed by DQB1 alleles

Other

The other DQA1 alleles have no defined serotype. There are 5 groups, DQA1*02, *03, *04, *05, *06. DQA1 within these groups are either invariant or produce the same α-chain subunit. DQA1*02 and DQA1*06 contain only one allele. DQA1*03 has three alleles which each produce nearly identical α³. For DQA1*05, the DQA1*0501 and DQA1*0505 produce identical α⁵. Other DQA1*05 exist that produce variant α^5var, but these are rare.

linked DQB1 allele
0201	0202	0303
0301
0302
0303	0301	0602
0401	0303	0401	0402
0501	0201
0505	0301
0601	0301
See haplotype table in HLA-DQ. Unbolded are rare haplotypes
Link to haplotypes can be followed by DQB1 alleles

See also

• Major histocompatibility complex
• Human leukocyte antigen
• HLA-DQ

Further reading

• Schmidt H, Williamson D, Ashley-Koch A . HLA-DR15 haplotype and multiple sclerosis: a HuGE review. . Am. J. Epidemiol. . 165 . 10 . 1097–109 . 2007 . 17329717 . 10.1093/aje/kwk118 . free .
• Marsh SG, Bodmer JG . HLA class II nucleotide sequences, 1992. . Tissue Antigens . 40 . 5 . 229–43 . 1993 . 1362295 . 10.1111/j.1399-0039.1992.tb02050.x .
• Piatier-Tonneau D, Gastinel LN, Amblard F, etal . Interaction of CD4 with HLA class II antigens and HIV gp120. . Immunogenetics . 34 . 2 . 121–8 . 1991 . 1869305 . 10.1007/BF00211424. 10116507 .
• Rosenstein Y, Burakoff SJ, Herrmann SH . HIV-gp120 can block CD4-class II MHC-mediated adhesion. . J. Immunol. . 144 . 2 . 526–31 . 1990 . 10.4049/jimmunol.144.2.526 . 1967269 . 23550626 . free .
• Bowman MR, MacFerrin KD, Schreiber SL, Burakoff SJ . Identification and structural analysis of residues in the V1 region of CD4 involved in interaction with human immunodeficiency virus envelope glycoprotein gp120 and class II major histocompatibility complex molecules. . Proc. Natl. Acad. Sci. U.S.A. . 87 . 22 . 9052–6 . 1991 . 1978941 . 55099 . 10.1073/pnas.87.22.9052 . free .
• Lee KW, Johnson AH, Hurley CK . Two divergent routes of evolution gave rise to the DRw13 haplotypes. . J. Immunol. . 145 . 9 . 3119–25 . 1990 . 10.4049/jimmunol.145.9.3119 . 2212675 . 19868100 .
• Todd JA, Fukui Y, Kitagawa T, Sasazuki T . The A3 allele of the HLA-DQA1 locus is associated with susceptibility to type 1 diabetes in Japanese. . Proc. Natl. Acad. Sci. U.S.A. . 87 . 3 . 1094–8 . 1990 . 2300572 . 53417 . 10.1073/pnas.87.3.1094 . 1990PNAS...87.1094T . free .
• Kao HT, Gregersen PK, Tang JC, etal . Molecular analysis of the HLA class II genes in two DRw6-related haplotypes, DRw13 DQw1 and DRw14 DQw3. . J. Immunol. . 142 . 5 . 1743–7 . 1989 . 10.4049/jimmunol.142.5.1743 . 2493052 . 31820831 . free .
• Gyllensten UB, Erlich HA . Ancient roots for polymorphism at the HLA-DQ alpha locus in primates. . Proc. Natl. Acad. Sci. U.S.A. . 86 . 24 . 9986–90 . 1990 . 2513578 . 298627 . 10.1073/pnas.86.24.9986 . free .
• Clayton LK, Sieh M, Pious DA, Reinherz EL . Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding. . Nature . 339 . 6225 . 548–51 . 1989 . 2543930 . 10.1038/339548a0 . 1989Natur.339..548C . 4246781 . free .
• Jonsson AK, Andersson L, Rask L . Complete sequences of DQA1 and DQB1 cDNA clones corresponding to the DQw4 specificity. . Immunogenetics . 30 . 3 . 232–4 . 1989 . 2777341 . 10.1007/BF02421214 . 28206170 .
• Diamond DC, Sleckman BP, Gregory T, etal . Inhibition of CD4+ T cell function by the HIV envelope protein, gp120. . J. Immunol. . 141 . 11 . 3715–7 . 1988 . 10.4049/jimmunol.141.11.3715 . 2846691 . 2607172 . free .
• Turco E, Care A, Compagnone-Post P, etal . Allelic forms of the alpha- and beta-chain genes encoding DQw1-positive heterodimers. . Immunogenetics . 26 . 4–5 . 282–90 . 1987 . 2888727 . 10.1007/BF00346523 . 44734030 .
• Hurley CK, Gregersen P, Steiner N, etal . Polymorphism of the HLA-D region in American blacks. A DR3 haplotype generated by recombination . J. Immunol. . 140 . 3 . 885–92 . 1988 . 10.4049/jimmunol.140.3.885 . 2892884 . 23340227 . free .
• Jonsson AK, Hyldig-Nielsen JJ, Servenius B, etal . Class II genes of the human major histocompatibility complex. Comparisons of the DQ and DX alpha and beta genes . J. Biol. Chem. . 262 . 18 . 8767–77 . 1987 . 10.1016/S0021-9258(18)47482-0 . 3036828 . free .
• Liu CP, Bach FH, Wu SK . Molecular studies of a rare DR2/LD-5a/DQw3 HLA class II haplotype. Multiple genetic mechanisms in the generation of polymorphic HLA class II genes . J. Immunol. . 140 . 10 . 3631–9 . 1988 . 10.4049/jimmunol.140.10.3631 . 3129499 . 20838749 . free .
• Lock CB, So AK, Welsh KI, etal . MHC class II sequences of an HLA-DR2 narcoleptic . Immunogenetics . 27 . 6 . 449–55 . 1988 . 3259543 . 10.1007/BF00364432 . 2338823 .
• Horn GT, Bugawan TL, Long CM, etal . Sequence analysis of HLA class II genes from insulin-dependent diabetic individuals . Hum. Immunol. . 21 . 4 . 249–63 . 1988 . 3372263 . 10.1016/0198-8859(88)90034-1 .
• Andrieu JM, Even P, Venet A . AIDS and related syndromes as a viral-induced autoimmune disease of the immune system: an anti-MHC II disorder. Therapeutic implications . AIDS Research . 2 . 3 . 163–74 . 1986 . 3489470 . 10.1089/aid.1.1986.2.163.
• Schiffenbauer J, Didier DK, Klearman M, etal . Complete sequence of the HLA DQ alpha and DQ beta cDNA from a DR5/DQw3 cell line . J. Immunol. . 139 . 1 . 228–33 . 1987 . 10.4049/jimmunol.139.1.228 . 3584986 . 27766754 . free .

Notes and References

1. Web site: Entrez Gene: HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1.
2. Lau M, Terasaki PI, Park MS . International Cell Exchange, 1994 . Clin Transpl . 467–88 . 1994 . 7547576 .