HLA-DR

heteropolypeptide
heteropolymer = MHC class II, DR
polymer_type = heterodimer
protein_type = cell surface receptor
function = Immune recognition and
antigen presentation


image_source = Illustration of DR with bound ligand (yellow)
SubunitCount = 5
subunit1 = α
gene1 = HLA-DRA
locus1 = Chromosome 6p21.31
subunit2 = β1
gene2 = HLA-DRB1
locus2 = " "
subunit3 = β3
gene3 = HLA-DRB3
locus3 = " "
subunit4 = β4
gene4 = HLA-DRB4
locus4 = " "
subunit5 = β5
gene5 = HLA-DRB5
locus5 = " "

HLA-DR is a major histocompatibility complex, MHC class II, cell surface receptorencoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31.The complex of HLA-DR and its ligand, a peptide of 9 amino acids in length or longer, constitutes a ligand for the T-cell receptor (TCR). HLA (human leukocyte antigens) were originally definedas cell surface antigens that mediate graft-versus-host disease, which resulted in therejection of tissue transplants in HLA-mismatched donors. Identification of theseantigens has led to greater success and longevity in organ transplant.

HLA-DR is also involved in several autoimmune conditions, disease susceptibilityand disease resistance. It is also closely linked to HLA-DQ and this linkage often makes it difficult to resolve the more causative factor in disease.

HLA-DR molecules are upregulated in response to signalling. In the instanceof an infection, the peptide (such as the staphlococcal enterotoxin I peptide show in the two illustrations) is bound into a DR molecule and presented to a few of a great many T-cellreceptors found on T-helper cells. These cells then bind to antigens on the surfaceof B-cells stimulating B-cell proliferation.

Function

thumb|left|150px|Illustration of DR receptor presenting antigento TCR on T-helper cellThe primary function of HLA-DR is to present peptide antigens, potentially foreignin origin, to the immune system for the purpose of eliciting or suppressing T-(helper)-cell responses that eventually lead to the production of antibodies against the same peptide antigen. Antigen presenting cells (macrophages, B-cells and dendritic cells) are the cells in which DR are typically found. Increased abundance of DR 'antigen' on the cell surface is often in response to stimulation, and, therefore, DR is also a marker for immune stimulation.

tructure

HLA-DR is a αβ heterodimer, cell surface receptor, each subunit contains 2 extracellular domains, a membrane spanning domain and a cytoplasmic tail. Both α and β chains are anchored in the membrane. The N-terminal domain of the mature protein forms an alpha-helix that constitutes the exposed part of the binding groove, the C-terminal cytoplasmic region interact with the other chain forming a beta-sheet under the binding groove spanning to the cell membrane. The majority of the peptide contact positions are in the 1st 80 residues of each chain.

Genetics

The genetics of HLA-DR is complex. HLA-DR is encoded by several loci and several 'genes' of different function at each locus. The DR α-chain is encoded by the HLA-DRA . Unlike the other DR loci functional variation in mature DRA gene products is absent. (Note: see table "Number of Variant Alleles HLA-DR Loci"- reduces the potential functional combinations from ~1400 to ~400 (table is not exact because new alleles are continually being added not all new alleles are functional variants of the mature subunits)).

The table provide below links to subpages with information about distribution, geneticlinkage and disease association for the HLA-DR serogroups.

Interlocus DRB Linkage

DRB1 is linked with other DRB loci in 4 ways

=Associated diseases=

=External links=
*

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Bénichou S, Benmerah A |title=The HIV nef and the Kaposi-sarcoma-associated virus K3/K5 proteins: "parasites"of the endocytosis pathway |journal=Med Sci (Paris) |volume=19 |issue= 1 |pages= 100–6 |year= 2003 |pmid= 12836198 |doi=
*cite journal | author=Tolstrup M, Ostergaard L, Laursen AL, "et al." |title=HIV/SIV escape from immune surveillance: focus on Nef. |journal=Curr. HIV Res. |volume=2 |issue= 2 |pages= 141–51 |year= 2004 |pmid= 15078178 |doi=
*cite journal | author=Anderson JL, Hope TJ |title=HIV accessory proteins and surviving the host cell. |journal=Current HIV/AIDS reports |volume=1 |issue= 1 |pages= 47–53 |year= 2005 |pmid= 16091223 |doi=
*cite journal | author=Li L, Li HS, Pauza CD, "et al." |title=Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions. |journal=Cell Res. |volume=15 |issue= 11-12 |pages= 923–34 |year= 2006 |pmid= 16354571 |doi= 10.1038/sj.cr.7290370
*cite journal | author=Stove V, Verhasselt B |title=Modelling thymic HIV-1 Nef effects. |journal=Curr. HIV Res. |volume=4 |issue= 1 |pages= 57–64 |year= 2006 |pmid= 16454711 |doi=
*cite journal | author=Matsushima GK, Itoh-Lindstrom Y, Ting JP |title=Activation of the HLA-DRA gene in primary human T lymphocytes: novel usage of TATA and the X and Y promoter elements. |journal=Mol. Cell. Biol. |volume=12 |issue= 12 |pages= 5610–9 |year= 1992 |pmid= 1448091 |doi=
*cite journal | author=Schaiff WT, Hruska KA, McCourt DW, "et al." |title=HLA-DR associates with specific stress proteins and is retained in the endoplasmic reticulum in invariant chain negative cells. |journal=J. Exp. Med. |volume=176 |issue= 3 |pages= 657–66 |year= 1992 |pmid= 1512535 |doi=
*cite journal | author=Piatier-Tonneau D, Gastinel LN, Amblard F, "et al." |title=Interaction of CD4 with HLA class II antigens and HIV gp120. |journal=Immunogenetics |volume=34 |issue= 2 |pages= 121–8 |year= 1991 |pmid= 1869305 |doi=
*cite journal | author=Nong Y, Kandil O, Tobin EH, "et al." |title=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. |journal=Cell. Immunol. |volume=132 |issue= 1 |pages= 10–6 |year= 1991 |pmid= 1905983 |doi=
*cite journal | author=Rosenstein Y, Burakoff SJ, Herrmann SH |title=HIV-gp120 can block CD4-class II MHC-mediated adhesion. |journal=J. Immunol. |volume=144 |issue= 2 |pages= 526–31 |year= 1990 |pmid= 1967269 |doi=
*cite journal | author=Callahan KM, Fort MM, Obah EA, "et al." |title=Genetic variability in HIV-1 gp120 affects interactions with HLA molecules and T cell receptor. |journal=J. Immunol. |volume=144 |issue= 9 |pages= 3341–6 |year= 1990 |pmid= 1970352 |doi=
*cite journal | author=Bowman MR, MacFerrin KD, Schreiber SL, Burakoff SJ |title=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. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=87 |issue= 22 |pages= 9052–6 |year= 1991 |pmid= 1978941 |doi=
*cite journal | author=Koppelman B, Cresswell P |title=Rapid nonlysosomal degradation of assembled HLA class II glycoproteins incorporating a mutant DR alpha-chain. |journal=J. Immunol. |volume=145 |issue= 8 |pages= 2730–6 |year= 1990 |pmid= 2212658 |doi=
*cite journal | author=Clayton LK, Sieh M, Pious DA, Reinherz EL |title=Identification of human CD4 residues affecting class II MHC versus HIV-1 gp120 binding. |journal=Nature |volume=339 |issue= 6225 |pages= 548–51 |year= 1989 |pmid= 2543930 |doi= 10.1038/339548a0
*cite journal | author=Diamond DC, Sleckman BP, Gregory T, "et al." |title=Inhibition of CD4+ T cell function by the HIV envelope protein, gp120. |journal=J. Immunol. |volume=141 |issue= 11 |pages= 3715–7 |year= 1988 |pmid= 2846691 |doi=
*cite journal | author=Tjernlund U, Scheynius A, Johansson C, "et al." |title=T-cell response to purified protein derivative after removal of Langerhans' cells from epidermal cell suspensions containing keratinocytes expressing class II transplantation antigens. |journal=Scand. J. Immunol. |volume=28 |issue= 6 |pages= 667–73 |year= 1989 |pmid= 3266023 |doi=
*cite journal | author=Andrieu JM, Even P, Venet A |title=AIDS and related syndromes as a viral-induced autoimmune disease of the immune system: an anti-MHC II disorder. Therapeutic implications. |journal=AIDS research |volume=2 |issue= 3 |pages= 163–74 |year= 1986 |pmid= 3489470 |doi=
*cite journal | author=Das HK, Lawrance SK, Weissman SM |title=Structure and nucleotide sequence of the heavy chain gene of HLA-DR. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=80 |issue= 12 |pages= 3543–7 |year= 1983 |pmid= 6304715 |doi=
*cite journal | author=Schamboeck A, Korman AJ, Kamb A, Strominger JL |title=Organization of the transcriptional unit of a human class II histocompatibility antigen: HLA-DR heavy chain. |journal=Nucleic Acids Res. |volume=11 |issue= 24 |pages= 8663–75 |year= 1984 |pmid= 6324094 |doi=
*cite journal | author=Das HK, Biro PA, Cohen SN, "et al." |title=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. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=80 |issue= 6 |pages= 1531–5 |year= 1983 |pmid= 6403940 |doi=

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