Affinage

HLA-DRA

HLA class II histocompatibility antigen, DR alpha chain · UniProt P01903

Length
254 aa
Mass
28.6 kDa
Annotated
2026-04-28
80 papers in source corpus 29 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HLA-DRA encodes the non-polymorphic α-chain of the MHC class II HLA-DR heterodimer, which presents peptide antigens to CD4+ T cells and participates in thymic negative selection of superantigen-reactive T cells (PMID:8420827, PMID:9510368). Transcription of HLA-DRA is governed by a modular proximal promoter containing W, X1, X2, and Y boxes that must be stereospecifically aligned; RFX binds the X1 box to establish an open chromatin state, NF-Y occupies the Y box, and the master coactivator CIITA recruits distinct histone acetyltransferase (GCN5/ATAC/STAGA) and methyltransferase (MLL1) complexes to drive H3 and H4 modifications that constitute a stable epigenetic memory of activation (PMID:2467188, PMID:1331098, PMID:11429551, PMID:22701520). IFN-γ-inducible expression proceeds through CIITA-dependent enhancement of X1/X2 occupancy, whereas TLR signaling activates HLA-DRA via NF-κB, and Oct-1 can repress the gene in Rb-defective tumor cells by assembling the DRAN complex that excludes NF-Y (PMID:1502171, PMID:16619292, PMID:15105429). An alternative splice isoform lacking 25 extracellular amino acids (rs8084) is retained in the ER but associates with canonical HLA-DR heterodimers through its peptide-binding domain, allosterically modifying peptide-groove conformation (PMID:32986852, PMID:35218721).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1989 High

    Establishing that the trans-acting factor RF-X is required for an open chromatin state at HLA-DRA resolved how promoter accessibility is controlled: without RF-X (as in hereditary class II immunodeficiency), DNase I-hypersensitive sites at the DRA promoter are lost, showing that factor binding creates the permissive chromatin architecture necessary for transcription.

    Evidence DNase I hypersensitivity mapping in normal vs. class II-deficient B cells and IFN-γ-induced fibroblasts

    PMID:2467188

    Open questions at the time
    • Identity of RF-X subunits not yet molecularly resolved at this stage
    • Whether RF-X binding is sufficient or only necessary for transcription unclear
    • Mechanism by which RF-X remodels chromatin not determined
  2. 1990 High

    Mapping the cis-regulatory architecture of HLA-DRA showed that X-box binding proteins mediate both positive and negative regulation through multiple upstream elements (W, V, X), and that the Y box is the dominant element for in vitro transcription, while the octamer does not function via OTF-2 as in immunoglobulin promoters.

    Evidence Promoter deletions, substitution mutants, nuclease S1 protection, EMSA, in vitro transcription in B-cell and HeLa extracts

    PMID:2120707 PMID:2278044

    Open questions at the time
    • In vitro transcription system may not recapitulate chromatin-level regulation
    • Identity of Y-box binding factor not confirmed as NF-Y at this point
  3. 1991 High

    Dissection of the X box into functionally distinct X1 and X2 sub-elements, bound by RFX and a separate X2BP respectively, revealed that HLA-DRA transcription integrates at least two independent DNA-binding activities at the X region, each with different class II promoter specificities.

    Evidence EMSA with nuclear proteins, single-basepair mutagenesis of X box, comparison of natural and recombinant RF-X binding

    PMID:1903200 PMID:1904083 PMID:1956787

    Open questions at the time
    • Molecular cloning of X2BP not achieved
    • Functional cooperativity between X1 and X2 factors not directly demonstrated
  4. 1992 High

    Stereospecific spacing between S, X, and Y elements was shown to be essential for both constitutive and IFN-γ-inducible DRA transcription, and IFN-γ acts by enhancing X1/X2 protein–DNA interactions on a poised promoter rather than by opening chromatin de novo, while cell-type-specific differences (astrocytes, glioblastoma, T cells) revealed distinct regulatory logics for the same promoter.

    Evidence Spacing/alignment mutant constructs in B cells and IFN-γ-treated fibroblasts; in vivo genomic footprinting across cell types; primary astrocyte transfection; primary T-cell reporter assays

    PMID:1331098 PMID:1448091 PMID:1454841 PMID:1502171 PMID:1560213 PMID:1588050

    Open questions at the time
    • Nature of IFNEX and TIC-X novel complexes in astrocytes not molecularly defined
    • Mechanism of T-cell-specific TATTA-dependent activation not connected to known X/Y pathway
  5. 1994 Medium

    Discovery of a 3′ UTR nuclear retention signal in HLA-DRA mRNA established a post-transcriptional layer of regulation: sequence-specific RNA–protein interactions partition DRA transcripts between nucleus and cytoplasm, adding a previously unknown control point beyond transcription.

    Evidence 3′ UTR deletion constructs, RNA fractionation, RNA–protein binding assays in multiple cell lines

    PMID:8028004

    Open questions at the time
    • Identity of the RNA-binding proteins mediating retention not determined
    • Physiological conditions that regulate nuclear-cytoplasmic partitioning unknown
    • Not independently replicated
  6. 1995 High

    Identification of far-upstream X′ and Y′ boxes bound by the same factors as the proximal elements, and purification of TRAX1 as a novel X1-box activator, expanded the regulatory landscape of HLA-DRA and indicated long-range interactions potentially forming chromatin loop structures.

    Evidence Affinity purification and in vitro transcription reconstitution for TRAX1; DNase I footprinting and EMSA for far-upstream elements

    PMID:7784170 PMID:7799935

    Open questions at the time
    • TRAX1 gene identity not cloned
    • Stem-loop model for far-upstream interaction only supported by in vitro data at this stage
  7. 1996 Medium

    Demonstrating that Rb is specifically required for IFN-γ induction of HLA-DRA in tumor cells—and that Rb reconstitution rescues DRB but not DRA—revealed a locus-specific silencing mechanism in Rb-defective cancers, separating DRA regulation from general CIITA availability.

    Evidence Rb reconstitution in Rb-defective tumor cells, Northern blot, CIITA mRNA analysis, surface DR flow cytometry

    PMID:8786310

    Open questions at the time
    • Mechanism by which Rb acts specifically at DRA locus not identified
    • Single tumor cell line model
  8. 1999 Medium

    NF-Y was unambiguously confirmed as the factor binding both proximal Y and far-upstream Y′ boxes, and evidence for protein–protein interactions between proximal and distal element complexes supported a stem-loop chromatin architecture model for HLA-DRA regulation.

    Evidence Antibody supershift EMSA for NF-Y, DNase I footprinting of far-upstream region

    PMID:10385003

    Open questions at the time
    • Stem-loop structure not validated in vivo (e.g., 3C/4C)
    • Functional significance of long-range interaction for transcription not tested by mutagenesis
  9. 2001 High

    CIITA was shown to coordinate distinct histone acetyltransferase activities at the HLA-DRA promoter in vivo—its activation domain mutant selectively loses H3 but retains H4 acetylation—establishing that CIITA acts as a scaffold recruiting multiple chromatin-modifying enzymes rather than a single HAT.

    Evidence In vivo chromatin analysis with time-course histone acetylation and CIITA activation-domain mutants

    PMID:11429551

    Open questions at the time
    • Specific HAT enzymes responsible for H3 vs. H4 acetylation not identified in this study
    • Whether HAT recruitment is direct or via intermediary factors unknown
  10. 2004 High

    The Oct-1/DRAN complex was identified as a repressor that blocks NF-Y access to the HLA-DRA promoter in Rb-defective cells, mechanistically explaining the locus-specific silencing observed earlier and connecting Rb loss to epigenetic shutdown of DRA.

    Evidence Oct-1 antisense transformants, ChIP, EMSA, trichostatin A de-repression

    PMID:15105429

    Open questions at the time
    • Composition of DRAN complex beyond Oct-1 not fully defined
    • Whether DRAN operates at other MHC-II loci not tested
  11. 2006 High

    Revealing that TLR-triggered HLA-DRA induction requires NF-κB binding to the DRA promoter—distinct from IFN-γ-mediated CIITA-dependent induction—established two parallel transcriptional pathways converging on the same gene, explaining how innate immune signals upregulate MHC-II independently of CIITA.

    Evidence Dominant-negative CIITA and NF-κB, RNAi, promoter mutants, EMSA, ChIP in human B cells

    PMID:16619292

    Open questions at the time
    • NF-κB binding site in DRA promoter not precisely mapped relative to W/X/Y architecture
    • Whether NF-κB and CIITA pathways are mutually exclusive or additive not fully resolved
  12. 2012 High

    Systematic ChIP across the HLA-DRA gene body identified MLL1, GCN5, ATAC, and STAGA complexes as the histone-modifying machinery recruited by CIITA, with some MLL components (MLL1, ASH2L, RbBP5) being CIITA-independent; H3K4me3 and acetylation marks persist through cell divisions, constituting epigenetic memory of MHC-II activation.

    Evidence Dual cross-linking ChIP in IFN-γ-induced epithelial cells, B cells, and MHC-II mutant B cells

    PMID:22701520

    Open questions at the time
    • Mechanism of CIITA-independent MLL1 recruitment not determined
    • Whether epigenetic memory requires continuous RFX occupancy not tested
  13. 2020 Medium

    Discovery that the rs8084 splice variant generates a short HLA-DRA isoform retained in the ER but capable of associating with canonical HLA-DR heterodimers revealed an unexpected protein-level regulatory mechanism by which alternative splicing can modify the functional conformation of surface MHC-II.

    Evidence Cellular trafficking experiments, co-expression with β-chain, ER localization assays, molecular dynamics simulations, mutagenesis of F76

    PMID:32986852 PMID:35218721

    Open questions at the time
    • In vivo functional consequence of sHLA-DRA on antigen presentation not demonstrated
    • Population-level impact of rs8084 on immune responses unknown
    • Single-lab findings not independently replicated
  14. 2024 Medium

    Cuproptosis-driven ROS was shown to upregulate HLA-DRA transcription dose-dependently, and high HLA-DRA levels promoted chemokine expression and T-cell infiltration that synergized with anti-PD-1 therapy in vivo, linking HLA-DRA expression to tumor immune microenvironment remodeling.

    Evidence In vitro dose-response, ROS measurement, in vivo mouse tumor model with anti-PD-1, qRT-PCR for chemokines

    PMID:38931345

    Open questions at the time
    • Transcriptional pathway from ROS to HLA-DRA not defined (CIITA vs. NF-κB involvement unknown)
    • Mouse model used murine system; direct human translational relevance not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the molecular identity and cloning of several DRA-specific trans-acting factors (TRAX1, X2BP, IFNEX, TIC-X); the in vivo validation of the proposed stem-loop chromatin architecture; the functional impact of the short HLA-DRA isoform on antigen presentation and T-cell responses; and the precise transcriptional pathway through which oxidative stress and cuproptosis activate HLA-DRA.
  • TRAX1/X2BP/IFNEX molecular identities remain unknown
  • Stem-loop model lacks chromosome conformation capture validation
  • sHLA-DRA functional impact on antigen presentation untested in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3
Localization
GO:0005783 endoplasmic reticulum 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 3
Partners
CIITAHLA-DRB1NF-YOCT1RELARFX1
Complex memberships
HLA-DR (DRA/DRB heterodimer)

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 CIITA coordinates multiple histone acetyltransferase activities at the HLA-DRA promoter in vivo: CIITA binding drives acetylation of both H3 and H4 histones, with a CIITA activation-domain mutant inducing H4 (at Lys8) but not H3 acetylation, indicating distinct HAT activities are recruited for each mark. In vivo chromatin analysis (time-course histone acetylation assays at HLA-DRA promoter), CIITA mutant expression Nature immunology High 11429551
1991 Two distinct X-box binding proteins regulate HLA-DRA transcription in B cells: RFX binds the X1 box (poorly to beta-chain gene promoters), while a separate factor X2BP binds the X2 box with high affinity and recognizes a different subset of class II promoters. Gel-mobility shift assays (EMSA), nuclear protein binding studies with HLA-DRA promoter fragments Nucleic acids research High 1956787
1992 IFN-γ induces HLA-DRA expression in glioblastoma cells by upregulating X1 and X2 box protein–DNA interactions on a poised promoter while leaving other promoter contacts (octamer, Y box) unchanged; the octamer site is occupied in lymphoid but not in glioblastoma cells despite an open chromatin state. In vivo genomic footprinting in multiple cell lines ± IFN-γ treatment Proceedings of the National Academy of Sciences of the United States of America High 1502171
1992 Constitutive and IFN-γ-inducible transcription of HLA-DRA requires stereospecific alignment between the S and X elements (spacing changes abolish activity regardless of helical alignment) and between X and Y elements; these three elements function through a common pathway, likely via direct or indirect protein complex formation. Transient transfection of spacing/alignment mutant DRA promoter constructs in B cells and IFN-γ-treated fibroblasts The Journal of biological chemistry High 1331098
1992 Single base-pair substitutions in the HLA-DRA X1 and X2 boxes functionally separate their contributions: X1 and X2 mutations differentially affect B-cell transcription versus IFN-γ induction in fibroblasts, and in vivo X-box protein occupancy correlates with transcriptional activity. Site-directed mutagenesis of DRA promoter, transient transfection in B cells and IFN-γ-treated fibroblasts, EMSA Journal of immunology High 1560213
1990 X-box binding proteins mediate both positive and negative transcriptional regulation of HLA-DRA via interaction with multiple upstream elements (W at −135 to −117, V at −193 to −179, and X box); gel-shift competition confirmed W- and V-bound proteins are the same as X-box-binding proteins. 5′ promoter deletions, substitution mutants, nuclease S1 protection assays, EMSA with competition Proceedings of the National Academy of Sciences of the United States of America High 2120707
1992 In primary astrocytes, IFN-γ regulation of HLA-DRA requires the S, X1 (but not X2), and Y promoter elements; IFN-γ induces a novel X-element-binding nuclear factor (IFNEX) in astrocytes that may underlie IFN-γ-mediated class II induction in this cell type. Site-specific mutagenesis of DRA promoter, transient transfection in primary astrocytes, EMSA with nuclear extracts Journal of immunology Medium 1588050
1992 TNF-α synergizes with IFN-γ to activate HLA-DRA promoter activity through the W, X, and Y elements in astrocytes; combined cytokine treatment induces a novel, slower-mobility X-element DNA–protein complex (TIC-X) not seen with either cytokine alone. Transient transfection of DRA-CAT reporter in primary astrocytes, EMSA with nuclear extracts from cytokine-treated cells Proceedings of the National Academy of Sciences of the United States of America Medium 1454841
1989 The trans-acting factor RF-X binds to the HLA-DRA promoter and its absence (in hereditary class II immunodeficiency cells) abolishes two prominent DNase I-hypersensitive sites at the DRA promoter, linking RF-X binding to an open chromatin state necessary (but not sufficient) for DRA expression. DNase I hypersensitivity mapping in normal vs. class II-deficient B cells and IFN-γ-induced fibroblasts Molecular and cellular biology High 2467188
1991 RF-X binding to the HLA-DRA X1 box requires specific base pairs within the X box motif; single base-pair substitutions that eliminate RF-X binding also reduce expression, and natural/recombinant RF-X show identical binding-site specificity. EMSA with single-basepair substitution mutants of the DRA X box; comparison of natural and recombinant RF-X Nucleic acids research High 1903200
1991 Mutant B-cell line 6.1.6 lacks a specific X-box DNA–protein complex (X-A, containing proteins of ~22, 32, 82, and 92 kDa) and shows greatly reduced DRA promoter activity in transfection assays; the same complex is absent in some class II-immunodeficient patient cell lines, implicating an X-box binding protein defect. Transient transfection of DRA promoter fragments, EMSA, UV cross-linking of X-A complex components Journal of immunology Medium 1904083
2006 TLR-triggered (CpG-DNA and LPS) HLA-DRA induction in human B cells requires NF-κB binding to the DRA promoter in addition to CIITA; IFN-γ-induced DRA expression depends on CIITA rather than NF-κB, revealing a distinct TLR-specific mechanism for MHC-II regulation. Dominant-negative CIITA and NF-κB constructs, RNAi, promoter mutant analysis, EMSA, chromatin immunoprecipitation (ChIP) European journal of immunology High 16619292
2004 Oct-1 represses the IFN-γ-inducible HLA-DRA gene in Rb-defective tumor cells by assembling a protein complex (DRAN) that blocks NF-Y access to the DRA promoter; Oct-1 antisense and TSA-induced promoter reactivation confirmed direct Oct-1 occupancy of the endogenous DRA promoter. Oct-1 antisense transformants, chromatin immunoprecipitation (ChIP), in vitro DNA–protein binding (EMSA), trichostatin A treatment The Journal of biological chemistry High 15105429
2012 Active HLA-DRA transcription is accompanied by nucleosome depletion at the proximal regulatory region and distribution of histone methylation (H3K4me3) and acetylation marks across the gene body; these modifications depend on RFX and CIITA binding, are stable through cell divisions after stimulus removal (epigenetic memory), and are laid down by MLL1 methyltransferase and GCN5 acetyltransferase complexes (ATAC/STAGA); some MLL complex components (MLL1, ASH2L, RbBP5) are CIITA-independent. Chromatin immunoprecipitation (ChIP) including dual cross-linking ChIP for histone-modifying complexes, in IFN-γ-induced epithelial cells, B cells, and B-cell MHC-II mutants PloS one High 22701520
1995 TRAX1, a novel X1-box-binding protein distinct from RFX1/NF-Xc/NF-X, was affinity-purified from HeLa nuclear extracts and shown by in vitro transcription assay to specifically activate HLA-DRA transcription; UV cross-linking estimated ~40 kDa; methylation interference showed TRAX1 contacts the 5′ end of the X1 box at −109/−108 with hypersensitive sites at −114/−113/−97. Affinity purification, in vitro transcription assay, EMSA, UV cross-linking, methylation interference Molecular and cellular biology High 7799935
1993 hXBP-1 (a b-zip transcription factor) regulates HLA-DRA expression; the hXBP-1 promoter contains an X2-identical element (hX2) essential for hXBP-1 autoregulation; protein complexes that bind hX2 in the hXBP-1 promoter cross-compete with those binding the X2 element of the DRA promoter, and both promoters share a downstream Y-box element, demonstrating shared regulatory logic. Promoter deletion/mutagenesis, EMSA with cross-competition, chromosomal mapping of hXBP-1 pseudogene vs. functional gene The Journal of biological chemistry Medium 8349596
1990 In vitro transcription of the HLA-DRA promoter in B-cell vs. HeLa extracts shows complete dependence on the Y box (deletion reduces transcription by 95%) and partial dependence on the X box; the DRA octamer element does not activate transcription via OTF-2 in the same manner as immunoglobulin promoters in B cells. In vitro transcription assay with B-cell and HeLa cell nuclear extracts, 5′ deletion and internal deletion constructs Tissue antigens Medium 2278044
1994 A sequence in the 3′ UTR of HLA-DRA mRNA functions as a nuclear retention signal; deletion of this region abrogates binding of compartmentalized nuclear/cytoplasmic proteins and releases DRA mRNA into the cytoplasm, indicating regulated nucleo-cytoplasmic partitioning of DRA transcripts by sequence-specific RNA–protein interactions. Transient transfection of DRA constructs with 3′ UTR deletions, RNA fractionation, RNA–protein binding assays in multiple cell lines Journal of molecular biology Medium 8028004
1992 HLA-DRA expression in primary T lymphocytes upon mitogenic/antigenic activation is driven by a proximal 43-bp promoter element containing a TATTA motif; addition of upstream X and Y elements augments the response but can also suppress it in certain activation states; this is mechanistically distinct from transformed cell lines where X and Y are essential for basal expression. Transient transfection of DRA-CAT reporter constructs into primary human T lymphocytes, TATTA mutation, activation with mitogens/antigens Molecular and cellular biology Medium 1448091
1996 The retinoblastoma (Rb) protein is required for IFN-γ induction of HLA-DRA (and HLA-DRB) mRNA in tumor cells; in Rb-defective non-small cell lung carcinoma H2009 cells, reconstitution of Rb rescues DRB but not DRA inducibility, demonstrating a specific defect at the DRA locus independent of general CIITA induction. Rb reconstitution in RB-defective tumor cells, IFN-γ treatment, Northern analysis of class II mRNA, CIITA mRNA analysis, surface DR flow cytometry Journal of immunology Medium 8786310
1993 HLA-DRA transgenic mice expressing the DR alpha chain (as a mixed DR alpha/E beta heterodimer) demonstrate that the DR alpha/E beta pair supports negative selection (clonal deletion) of T cells bearing V beta 5, V beta 6, V beta 7, and V beta 11, with deletion efficiency correlating with the proportion of DR alpha-positive APCs; thymic epithelial cell expression of DR alpha E beta is sufficient for clonal deletion of superantigen-reactive T cells. Transgenic mouse models with X-linked HLA-DRA, T-cell repertoire analysis (V beta deletion), mixed lymphocyte reaction Immunogenetics; European journal of immunology Medium 8100779 8420827
1998 HLA-DRA1*0101/DRB1*0401 heterodimer expressed in Drosophila cells can present peptides to DRB1*0401-restricted T cells; Drosophila-expressed molecules have reduced N-linked glycosylation, higher peptide-binding capacity, and can be stabilized by high-affinity peptides, indicating the heterodimer's peptide-binding function does not require mammalian glycosylation. Recombinant expression in Drosophila Schneider 2 cells, flow cytometry, peptide-binding assays, SDS-PAGE, T-cell stimulation assay Tissue antigens Medium 9510368
2020 A splice acceptor variant (rs8084) in HLA-DRA mediates transcription of an alternative α-chain isoform lacking 25 amino acids in its extracellular domain; this short isoform cannot reach the cell surface (trapped in the ER and degraded) but retains the ability to bind the β-chain and can be transported to the membrane via interaction with the peptide-binding site of canonical HLA heterodimers. Molecular dynamics simulation, cellular trafficking experiments, co-expression with β-chain, endoplasmic reticulum localization assays, immunoprecipitation Immunology Medium 32986852
2022 The short HLA-DRA isoform (sHLA-DRA, lacking 25 aa) binds to the outer domain of the HLA-DR2 peptide-binding site via a loop region (R69–G83) exposed only in the short isoform; F76 is critical for binding; sHLA-DRA allosterically modifies the peptide-binding pocket conformation of the canonical heterodimer. Atomistic molecular dynamics simulations, experimental mutagenesis of F76, binding assays Archives of biochemistry and biophysics Medium 35218721
1995 A far-upstream region of HLA-DRA contains X′ and Y′ boxes oriented in the opposite direction to the proximal X and Y boxes; DNase I footprinting and EMSA show these are specifically recognized by the same nuclear proteins that bind the proximal X and Y boxes, suggesting long-range regulatory interactions. DNase I footprinting, EMSA, sequence analysis and CpG analysis of far-upstream region Nucleic acids research Medium 7784170
1999 Nuclear proteins bound to the far-upstream Y′ and X′ boxes of HLA-DRA can interact with proteins bound to the proximal Y and X boxes to form a stem-loop secondary structure; NF-Y was unambiguously identified as one of the proteins binding both Y and Y′ boxes by antibody supershift assay. Gel retardation (EMSA), DNase I footprinting, antibody supershift for NF-Y Biochimie Medium 10385003
2024 Cuproptosis upregulates HLA-DRA expression at the transcriptional level (dose-dependently, via reactive oxygen species production), and high HLA-DRA levels promote chemokine expression (CCL5, CXCL9, CXCL10) and CD4+/CD8+ T-cell infiltration, synergizing with anti-PD-1 therapy in vivo to inhibit tumor growth. In vitro dose-response experiments, ROS measurement, in vivo mouse tumor model with anti-PD-1, immunohistochemistry, qRT-PCR for chemokines Pharmaceuticals Medium 38931345
2026 HLA-DRA regulates radiosensitivity of nasal mucosal epithelial cells: KO (CRISPR/Cas9) reduces apoptosis and suppresses IFN-γ and IL-6 expression after irradiation, while OE increases apoptosis and cytokine production; combined IL-6 and IFN-γ stimulation activates JAK-STAT signaling (STAT phosphorylation), placing HLA-DRA upstream of JAK-STAT pathway activation in radiation-induced sinusitis. CRISPR/Cas9 KO and OE of HLA-DRA in nasal epithelial cells, colony formation assay, CCK-8, flow cytometry for apoptosis, RT-qPCR, ELISA for cytokines, Western blot for STAT phosphorylation Zhonghua er bi yan hou tou jing wai ke za zhi Medium 41956771

Source papers

Stage 0 corpus · 80 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 CIITA coordinates multiple histone acetylation modifications at the HLA-DRA promoter. Nature immunology 151 11429551
1991 Two B cell factors bind the HLA-DRA X box region and recognize different subsets of HLA class II promoters. Nucleic acids research 73 1956787
1992 In vivo footprint analysis of the HLA-DRA gene promoter: cell-specific interaction at the octamer site and up-regulation of X box binding by interferon gamma. Proceedings of the National Academy of Sciences of the United States of America 68 1502171
2014 HLA-DRA variants predict penicillin allergy in genome-wide fine-mapping genotyping. The Journal of allergy and clinical immunology 65 25224099
1992 Single base pair substitutions within the HLA-DRA gene promoter separate the functions of the X1 and X2 boxes. Journal of immunology (Baltimore, Md. : 1950) 64 1560213
2010 Greater expression of TLR2, TLR4, and IL6 due to negative energy balance is associated with lower expression of HLA-DRA and HLA-A in bovine blood neutrophils after intramammary mastitis challenge with Streptococcus uberis. Functional & integrative genomics 59 20072847
1992 Structural constraints within a trimeric transcriptional regulatory region. Constitutive and interferon-gamma-inducible expression of the HLA-DRA gene. The Journal of biological chemistry 50 1331098
2013 Preliminary results in quantitation of HLA-DRA by real-time PCR: a promising approach to identify immunosuppression in sepsis. Critical care (London, England) 48 24093602
1990 X-box-binding proteins positively and negatively regulate transcription of the HLA-DRA gene through interaction with discrete upstream W and V elements. Proceedings of the National Academy of Sciences of the United States of America 46 2120707
1992 Usage of primary cells to delineate IFN-gamma-responsive DNA elements in the HLA-DRA promoter and to identify a novel IFN-gamma-enhanced nuclear factor. Journal of immunology (Baltimore, Md. : 1950) 39 1588050
1991 Transcriptional regulation of the HLA-DRA gene. Critical reviews in immunology 39 1930684
1989 Inherited immunodeficiency with a defect in a major histocompatibility complex class II promoter-binding protein differs in the chromatin structure of the HLA-DRA gene. Molecular and cellular biology 39 2467188
1996 Apoptosis-independent retinoblastoma protein rescue of HLA class II messenger RNA IFN-gamma inducibility in non-small cell lung carcinoma cells. Lack of surface class II expression associated with a specific defect in HLA-DRA induction. Journal of immunology (Baltimore, Md. : 1950) 38 8786310
1992 Localization of IFN-gamma receptor in first trimester placenta to trophoblasts but lack of stimulation of HLA-DRA, -DRB, or invariant chain mRNA expression by IFN-gamma. Journal of immunology (Baltimore, Md. : 1950) 38 1401907
1991 Defective HLA DRA X box binding in the class II transactive transcription factor mutant 6.1.6 and in cell lines from class II immunodeficient patients. Journal of immunology (Baltimore, Md. : 1950) 36 1904083
1991 The W element is a positive regulator of HLA-DRA transcription in various DR+ cell types. Journal of immunology (Baltimore, Md. : 1950) 36 1991973
2006 Direct role of NF-kappaB activation in Toll-like receptor-triggered HLA-DRA expression. European journal of immunology 35 16619292
1992 Tumor necrosis factor alpha response elements in the HLA-DRA promoter: identification of a tumor necrosis factor alpha-induced DNA-protein complex in astrocytes. Proceedings of the National Academy of Sciences of the United States of America 32 1454841
1991 Regulatory factor-X binding to mutant HLA-DRA promoter sequences. Nucleic acids research 31 1903200
2019 Insights into the polymorphism in HLA-DRA and its evolutionary relationship with HLA haplotypes. HLA 28 31617688
2022 HLA class II molecule HLA-DRA identifies immuno-hot tumors and predicts the therapeutic response to anti-PD-1 immunotherapy in NSCLC. BMC cancer 27 35794593
1995 A novel Creb family gene telomeric of HLA-DRA in the HLA complex. Genomics 25 8586413
2010 Multiple sclerosis risk markers in HLA-DRA, HLA-C, and IFNG genes are associated with sex-specific childhood leukemia risk. Autoimmunity 23 21067287
2003 Relative quantification of HLA-DRA1 and -DQA1 expression by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). European journal of immunogenetics : official journal of the British Society for Histocompatibility and Immunogenetics 23 12648283
2004 Oct-1 maintains an intermediate, stable state of HLA-DRA promoter repression in Rb-defective cells: an Oct-1-containing repressosome that prevents NF-Y binding to the HLA-DRA promoter. The Journal of biological chemistry 22 15105429
2022 Expression of NOTCH1, NOTCH4, HLA-DMA and HLA-DRA is synergistically associated with T cell exclusion, immune checkpoint blockade efficacy and recurrence risk in ER-negative breast cancer. Cellular oncology (Dordrecht, Netherlands) 21 35543859
2014 HLA-DRA is associated with Parkinson's disease in Iranian population. International journal of immunogenetics 19 25319953
1992 Activation of the HLA-DRA gene in primary human T lymphocytes: novel usage of TATA and the X and Y promoter elements. Molecular and cellular biology 19 1448091
2019 Genetic Variation Within the HLA-DRA1 Gene Modulates Susceptibility to Type 1 Diabetes in HLA-DR3 Homozygotes. Diabetes 18 30962219
1991 Description of a polymorphism in the regulatory region of the HLA-DRA gene. Human immunology 18 1685491
2022 CD74 and HLA-DRA in Cervical Carcinogenesis: Potential Targets for Antitumour Therapy. Medicina (Kaunas, Lithuania) 17 35208514
1990 Functional analysis of cis-linked regulatory sequences in the HLA DRA promoter by transcription in vitro. Tissue antigens 17 2278044
2017 New variants near RHOJ and C2, HLA-DRA region and susceptibility to endometriosis in the Polish population-The genome-wide association study. European journal of obstetrics, gynecology, and reproductive biology 16 28881265
2012 Multiple histone methyl and acetyltransferase complex components bind the HLA-DRA gene. PloS one 16 22701520
1998 Functional characterization of HLA-DRA1*0101/DRB1*0401 molecules expressed in Drosophila melanogaster cells. Tissue antigens 16 9510368
1993 The regulatory gene, hXBP-1, and its target, HLA-DRA, utilize both common and distinct regulatory elements and protein complexes. The Journal of biological chemistry 16 8349596
2013 Reaffirmation of GAK, but not HLA-DRA, as a Parkinson's disease susceptibility gene in a Taiwanese population. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 15 24039160
2012 HLA-DRA polymorphisms associated with risk of nasal polyposis in asthmatic patients. American journal of rhinology & allergy 15 22391069
1999 HLA-DMB gene and HLA-DRA promoter region polymorphisms in Australian multiple sclerosis patients. Human immunology 15 10527398
2016 HLA-DRA/HLA-DRB5 polymorphism affects risk of sporadic ALS and survival in a southwest Chinese cohort. Journal of the neurological sciences 13 28131168
1993 T-cell repertoire in a strain of transgenic C57BL/6 mice with the HLA-DRA gene on the X-chromosome. Immunogenetics 13 8420827
1993 Mouse mammary tumor virus-mediated T-cell receptor negative selection in HLA-DRA transgenic mice. Human immunology 12 8244778
1994 Control of nucleo-cytoplasmic HLA-DRA mRNA partitioning by interaction of a retention signal with compartmentalized proteins. Journal of molecular biology 11 8028004
1993 Restricted expression of transgenic HLA-DRA gene in thymic epithelial cells and its role in acquisition of T cell tolerance to self-superantigens and processed DR alpha-derived peptide. European journal of immunology 11 8100779
1991 Tissue-specific expression of the HLA-DRA gene in transgenic mice. Immunogenetics 11 1721044
1995 Affinity enrichment and functional characterization of TRAX1, a novel transcription activator and X1-sequence-binding protein of HLA-DRA. Molecular and cellular biology 10 7799935
2024 Improved Immunotherapy Outcomes via Cuproptosis Upregulation of HLA-DRA Expression: Promoting the Aggregation of CD4+ and CD8+T Lymphocytes in Clear Cell Renal Cell Carcinoma. Pharmaceuticals (Basel, Switzerland) 9 38931345
1995 Sequencing of an upstream region of the human HLA-DRA gene containing X' and Y' boxes. Nucleic acids research 9 7784170
2022 HLA-DRA Gene Polymorphisms Are Associated with Graves' Disease as an Autoimmune Thyroid Disease. BioMed research international 8 36132072
2021 Tri-SNP polymorphism in the intron of HLA-DRA1 affects type 1 diabetes susceptibility in the Finnish population. Human immunology 8 34311991
1991 Transcriptional regulation of HLA-DRA gene. Research in immunology 8 1754710
1997 HLA-DRA promoter polymorphism and diversity generation within the immune system. Human genetics 7 9187677
2020 Analysis of Single Nucleotide Polymorphisms in HLA-DRA, IL2RA , and HMGB1 Genes in Multiple Sclerosis. Reports of biochemistry & molecular biology 6 33178870
2017 Expression of HLA-DRA and CD74 mRNA in whole blood during the course of complicated and uncomplicated Staphylococcus aureus bacteremia. Microbiology and immunology 6 28862321
2022 Genetic polymorphism of HLA-DRA and alcohol consumption affect hepatitis development in the Korean population. Genes & genomics 4 35895219
2020 A splice acceptor variant in HLA-DRA affects the conformation and cellular localization of the class II DR alpha-chain. Immunology 4 32986852
2015 Association analysis of HLA-DRA in Chinese patients with sporadic Parkinson's disease. International journal of physiology, pathophysiology and pharmacology 4 27073595
2002 The HLA-DRA*0102 allele: correct nucleotide sequence and associated HLA haplotypes. Tissue antigens 4 12445311
1999 Analysis of the human HLA-DRA gene upstream region: evidence for a stem-loop array directed by nuclear factors. Biochimie 4 10385003
1997 In vitro and in vivo evidence for high frequency of I-Ab-reactive CD4+ T cells in HLA-DQ or HLA-DRA transgenic mice lacking endogenous MHC class I and/or class II expression. Journal of immunology (Baltimore, Md. : 1950) 4 9378957
2024 Changes in expression of VGF, SPECC1L, HLA-DRA and RANBP3L act with APOE E4 to alter risk for late onset Alzheimer's disease. Scientific reports 3 38942763
2022 Possible Relationship between the HLA-DRA1 Intron Haplotype of Three Single-Nucleotide Polymorphisms in Intron 1 of the HLA-DRA1 Gene and Autoantibodies in Children at Increased Genetic Risk for Autoimmune Type 1 Diabetes. ImmunoHorizons 3 35981747
2012 Common variants in HLA-DRA gene are associated with alcohol dependence in two Caucasian samples. Journal of molecular neuroscience : MN 3 22890421
2006 Korean BAC library construction and characterization of HLA-DRA, HLA-DRB3. Journal of biochemistry and molecular biology 3 16889686
2021 Identification of three novel HLA-DRA alleles by next-generation sequencing. HLA 2 34402606
2009 Technological advances in the study of HLA-DRA promoter regulation: extending the functions of CIITA, Oct-1, Rb, and RFX. Acta biochimica et biophysica Sinica 2 19280058
2005 Modular usage of the HLA-DRA promoter in extra-hematopoietic and hematopoietic cell types of transgenic mice. The FEBS journal 2 15955077
2025 Effects of HLA-DRA, HLA-DQA1 and IL-6 Gene Variations to Glatiramer Acetate Resistance in Multiple Sclerosis Patients. Biochemical genetics 1 40072812
2022 A short HLA-DRA isoform binds the HLA-DR2 heterodimer on the outer domain of the peptide-binding site. Archives of biochemistry and biophysics 1 35218721
2020 The rs3129882/rs4248166 in HLA-DRA and rs34372695 in SYT11 are not associated with sporadic Parkinson's disease in Central Chinese population. The International journal of neuroscience 1 32253955
2026 Polymorphisms in intron 1 of HLA-DRA differentially associate with type 1 diabetes and celiac disease and implicate involvement of complement system genes C4A and C4B. eLife 0 41627183
2026 Single-nucleus and machine-learning integration identifies HLA-DRA and FTL as immune-metabolic axes and traditional Chinese medicine-targetable hubs in calcific aortic valve disease. Journal of computer-aided molecular design 0 41721874
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2026 Identification of the Novel HLA-DRA*01:20 Allele by Single Molecule, Real-Time DNA Sequencing. HLA 0 41989255
2025 Association of HLA-DRA, HLA-DQA1, and IL-6 gene variations with susceptibility to multiple sclerosis. Molecular biology reports 0 40643781
2025 Role of HLA-DRA-CREB3L4 regulatory axis in the pathogenesis of ovarian endometriosis: Inhibition of CREB3L4 expression by HLA-DRA increases the risk of disease. Journal of reproductive immunology 0 41232153
2023 The Human Brainome: changes in expression of VGF, SPECC1L, HLA-DRA and RANBP3L act with APOE E4 to alter risk for late onset Alzheimer's disease. Research square 0 38168398
2003 Identification of a novel DNase I hypersensitive site within the far upstream region of the human HLA-DRA gene. International journal of molecular medicine 0 14612968
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1991 Methylation state of the human HLA-DRa gene in transgenic mice. Cytotechnology 0 22358954