HLA-DRA explained

HLA class II histocompatibility antigen, DR alpha chain is a protein that in humans is encoded by the HLA-DRA gene.^[1] HLA-DRA encodes the alpha subunit of HLA-DR. Unlike the alpha chains of other Human MHC class II molecules, the alpha subunit is practically invariable. However it can pair with, in any individual, the beta chain from 3 different DR beta loci, DRB1, and two of any DRB3, DRB4, or DRB5 alleles. Thus there is the potential that any given individual can form 4 different HLA-DR isoforms (2 alleles of DRB1 and two alleles from DRB3, DRB4 or DRB5).

Function

The polypeptide subunit encoded by this gene belongs to the HLA class II alpha chain paralogues. The class II protein is a heterodimer consisting of an alpha (DRα) and a beta chain (DRβ), 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 is approximately 33-35 kDa and its gene contains 5 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. DRA does not have polymorphisms in the peptide binding part and acts as the sole alpha chain for DRB1, DRB3, DRB4 and DRB5.^[1]

Alleles

There are two different HLA-DRA chains in the human population coded by three different DRA alleles:

DRA*01:01 DRA*01:02:01 DRA*01:02:02

See also

• HLA-DR

Further reading

• Bénichou S, Benmerah A . [The HIV nef and the Kaposi-sarcoma-associated virus K3/K5 proteins: "parasites"of the endocytosis pathway] . Med Sci (Paris) . 19 . 1 . 100–6 . 2003 . 12836198 . 10.1051/medsci/2003191100 . free .
• Tolstrup M, Ostergaard L, Laursen AL, etal . HIV/SIV escape from immune surveillance: focus on Nef. . Curr. HIV Res. . 2 . 2 . 141–51 . 2004 . 15078178 . 10.2174/1570162043484924 .
• Anderson JL, Hope TJ . HIV accessory proteins and surviving the host cell. . Current HIV/AIDS Reports . 1 . 1 . 47–53 . 2005 . 16091223 . 10.1007/s11904-004-0007-x . 34731265 .
• Li L, Li HS, Pauza CD, etal . Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions. . Cell Res. . 15 . 11–12 . 923–34 . 2006 . 16354571 . 10.1038/sj.cr.7290370 . free .
• Stove V, Verhasselt B . Modelling thymic HIV-1 Nef effects. . Curr. HIV Res. . 4 . 1 . 57–64 . 2006 . 16454711 . 10.2174/157016206775197583 .
• Matsushima GK, Itoh-Lindstrom Y, Ting JP . Activation of the HLA-DRA gene in primary human T lymphocytes: novel usage of TATA and the X and Y promoter elements. . Mol. Cell. Biol. . 12 . 12 . 5610–9 . 1992 . 1448091 . 10.1128/MCB.12.12.5610. 360500 .
• Schaiff WT, Hruska KA, McCourt DW, etal . HLA-DR associates with specific stress proteins and is retained in the endoplasmic reticulum in invariant chain negative cells. . J. Exp. Med. . 176 . 3 . 657–66 . 1992 . 1512535 . 10.1084/jem.176.3.657 . 2119345 .
• 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 .
• Nong Y, Kandil O, Tobin EH, etal . The HIV core protein p24 inhibits interferon-gamma-induced increase of HLA-DR and cytochrome b heavy chain mRNA levels in the human monocyte-like cell line THP1. . Cell. Immunol. . 132 . 1 . 10–6 . 1991 . 1905983 . 10.1016/0008-8749(91)90002-S .
• 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 . free .
• Callahan KM, Fort MM, Obah EA, etal . Genetic variability in HIV-1 gp120 affects interactions with HLA molecules and T cell receptor. . J. Immunol. . 144 . 9 . 3341–6 . 1990 . 10.4049/jimmunol.144.9.3341 . 1970352 . 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 . 10.1073/pnas.87.22.9052 . 55099 . free .
• Koppelman B, Cresswell P . Rapid nonlysosomal degradation of assembled HLA class II glycoproteins incorporating a mutant DR alpha-chain. . J. Immunol. . 145 . 8 . 2730–6 . 1990 . 10.4049/jimmunol.145.8.2730 . 2212658 . 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 .
• 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 . free .
• Tjernlund U, Scheynius A, Johansson C, etal . T-cell response to purified protein derivative after removal of Langerhans' cells from epidermal cell suspensions containing keratinocytes expressing class II transplantation antigens. . Scand. J. Immunol. . 28 . 6 . 667–73 . 1989 . 3266023 . 10.1111/j.1365-3083.1988.tb01500.x . 25824282 .
• 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.
• Das HK, Lawrance SK, Weissman SM . Structure and nucleotide sequence of the heavy chain gene of HLA-DR. . Proc. Natl. Acad. Sci. U.S.A. . 80 . 12 . 3543–7 . 1983 . 6304715 . 10.1073/pnas.80.12.3543 . 394085 . 1983PNAS...80.3543D . free .
• Schamboeck A, Korman AJ, Kamb A, Strominger JL . Organization of the transcriptional unit of a human class II histocompatibility antigen: HLA-DR heavy chain. . Nucleic Acids Res. . 11 . 24 . 8663–75 . 1984 . 6324094 . 10.1093/nar/11.24.8663 . 326615 .
• Das HK, Biro PA, Cohen SN, etal . Use of synthetic oligonucleotide probes complementary to genes for human HLA-DR alpha and beta as extension primers for the isolation of 5'-specific genomic clones. . Proc. Natl. Acad. Sci. U.S.A. . 80 . 6 . 1531–5 . 1983 . 6403940 . 10.1073/pnas.80.6.1531 . 393635 . 1983PNAS...80.1531D . free .

Notes and References

1. Web site: Entrez Gene: HLA-DRA major histocompatibility complex, class II, DR alpha.