Details for: HLA DQB2

Gene ID: 3120

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: HLA DQB2

Ensembl ID: ENSG00000232629

Description: major histocompatibility complex, class II, DQ beta 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • Langerhans cell CL0000453
    CSI 21.9
    rCSI 33.45%
    PRS 99.22
  • CD1c-positive myeloid dendritic cell CL0002399
    CSI 18.12
    rCSI 21.89%
    PRS 99.09
  • dendritic cell, human CL0001056
    CSI 6.79
    rCSI 10.42%
    PRS 99.18
  • alveolar macrophage CL0000583
    CSI 6.67
    rCSI 10.99%
    PRS 98.19
  • inflammatory macrophage CL0000863
    CSI 3.84
    rCSI 6.57%
    PRS 99.83
  • alternatively activated macrophage CL0000890
    CSI 3.38
    rCSI 4.25%
    PRS 99.52
  • lung macrophage CL1001603
    CSI 3.16
    rCSI 7.05%
    PRS 99.31
  • myeloid leukocyte CL0000766
    CSI 2.62
    rCSI 2.42%
    PRS 98.51
  • mononuclear phagocyte CL0000113
    CSI 2.47
    rCSI 5.43%
    PRS 98.67
  • myeloid dendritic cell CL0000782
    CSI 2.02
    rCSI 2.93%
    PRS 99.61

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [HLA DQB2](/details-gene/3120) is a protein-coding gene located on chromosome 6 that encodes the beta 2 chain of the non-classical Major Histocompatibility Complex (MHC) class II molecule, HLA-DQ. Functionally, it is integral to the [adaptive immune response](/details-go/GO:0002250) ([GO:0002250](https://www.ebi.ac.uk/QuickGO/term/GO:0002250)), where it participates in the processing and presentation of exogenous antigens to T-lymphocytes. Expression data reveals a highly specialized role for [HLA DQB2](/details-gene/3120), with its significance overwhelmingly concentrated in professional antigen-presenting cells (APCs). It is a particularly strong marker for [Langerhans cell](/details-cell/CL0000453)s and [CD1c-positive myeloid dendritic cell](/details-cell/CL0002399)s. Research indicates that [HLA DQB2](/details-gene/3120) pairs with HLA-DQA2 to form a distinct, non-polymorphic MHC class II heterodimer specifically expressed in human [Langerhans cell](/details-cell/CL0000453)s, suggesting a unique function in tissue-specific immune surveillance ([Link](https://doi.org/10.4049/jimmunol.1103048)). ## Cellular Roles and Expression Landscape The expression profile of [HLA DQB2](/details-gene/3120) is tightly restricted to cells of the myeloid lineage responsible for antigen presentation, underscoring its specialized immunological function. **Overall**, the gene exhibits the highest significance in professional APCs that act as sentinels of the immune system. The most prominent expression is observed in: * [Langerhans cell](/details-cell/CL0000453) (CSI: 21.90), a tissue-resident dendritic cell of the epidermis. * [CD1c-positive myeloid dendritic cell](/details-cell/CL0002399) (CSI: 18.12), a subset of conventional dendritic cells crucial for initiating T cell responses. Beyond these top-ranking cell types, [HLA DQB2](/details-gene/3120) also shows significant expression in a broader range of APCs, including other [dendritic cell, human](/details-cell/CL0001056) populations and various macrophage subsets such as [alveolar macrophage](/details-cell/CL0000583) (CSI: 6.67), [inflammatory macrophage](/details-cell/CL0000863) (CSI: 3.84), and [alternatively activated macrophage](/details-cell/CL0000890) (CSI: 3.38). This pattern is consistent with its established role in the [Mhc class ii antigen presentation](/details-pathway/R-HSA-2132295) pathway. Notably, literature confirms that the co-expression of [HLA DQB2](/details-gene/3120) and HLA-DQA2 is a specific feature of human [Langerhans cell](/details-cell/CL0000453)s ([Link](https://doi.org/10.4049/jimmunol.1103048)), solidifying its identity as a key molecular marker for this cell type. ## Pathways and Molecular Function The molecular functions and pathway involvements of [HLA DQB2](/details-gene/3120) are central to the initiation and regulation of the adaptive immune response. As a component of the [Mhc class ii protein complex](/details-go/GO:0042613) ([GO:0042613](https://www.ebi.ac.uk/QuickGO/term/GO:0042613)), its primary function is [peptide antigen binding](/details-go/GO:0042605) ([GO:0042605](https://www.ebi.ac.uk/QuickGO/term/GO:0042605)) and presentation. This process is a cornerstone of the [Adaptive immune system](/details-pathway/R-HSA-1280218) ([R-HSA-1280218](https://reactome.org/content/detail/R-HSA-1280218)). The HLA-DQB2-containing complex is assembled within the cell and traffics through various membrane-bound compartments, including the [endoplasmic reticulum](/details-go/GO:0098553) ([GO:0098553](https://www.ebi.ac.uk/QuickGO/term/GO:0098553)), [Golgi membrane](/details-go/GO:0000139) ([GO:0000139](https://www.ebi.ac.uk/QuickGO/term/GO:0000139)), and endosomal/lysosomal compartments ([GO:0031902](https://www.ebi.ac.uk/QuickGO/term/GO:0031902)) before reaching the [plasma membrane](/details-go/GO:0005886) ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO:0005886)). On the cell surface, it presents processed exogenous peptide antigens to CD4+ T-helper cells. This interaction triggers downstream T-cell receptor ([Tcr signaling](/details-pathway/R-HSA-202403) ([R-HSA-202403](https://reactome.org/content/detail/R-HSA-202403))) and costimulatory pathways such as [Costimulation by the cd28 family](/details-pathway/R-HSA-388841) ([R-HSA-388841](https://reactome.org/content/detail/R-HSA-388841)), leading to the [positive regulation of t cell activation](/details-go/GO:0050870) ([GO:0050870](https://www.ebi.ac.uk/QuickGO/term/GO:0050870)). The gene's activity is also linked to cytokine signaling pathways, including [Interferon gamma signaling](/details-pathway/R-HSA-877300) ([R-HSA-877300](https://reactome.org/content/detail/R-HSA-877300)), which is known to upregulate MHC class II expression. ## Research Directions The unique characteristics of [HLA DQB2](/details-gene/3120), particularly its restricted expression and non-polymorphic nature, distinguish it from classical HLA genes and suggest specialized roles that warrant further investigation. **Proposed Hypotheses:** 1. Given its high conservation ([Link](https://doi.org/10.1007/bf00717908)) and specific expression in tissue-resident [Langerhans cell](/details-cell/CL0000453)s ([Link](https://doi.org/10.4049/jimmunol.1103048)), the HLA-DQA2/DQB2 complex may be specialized for presenting a conserved class of antigens, such as microbial-derived lipids, glycolipids, or highly conserved pathogen peptides, serving as a first line of defense in epithelial tissues. 2. The observation that the promoter region of [HLA DQB2](/details-gene/3120) lacks typical in vivo DNA-protein interactions ([Link](https://doi.org/10.1016/s0198-8859(01)00236-1)) suggests its expression is governed by cell-type-specific distal regulatory elements or epigenetic mechanisms that are exclusively active in [Langerhans cell](/details-cell/CL0000453)s and related dendritic cell lineages. **Experimental Approach:** To test the first hypothesis regarding the antigen repertoire of the HLA-DQA2/DQB2 molecule, an immunopeptidomics approach could be employed. This would involve isolating primary human [Langerhans cell](/details-cell/CL0000453)s from skin explants or differentiating them from CD34+ hematopoietic progenitors. The HLA-DQA2/DQB2 complexes would be affinity-purified using a specific antibody, followed by acid elution of bound ligands. The eluted molecules would then be analyzed by high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify the sequence and nature of the presented peptides or other ligands. The resulting repertoire could be compared to that of classical HLA-DR or HLA-DQ molecules from the same cells to uncover unique binding motifs or antigen classes specific to the HLA-DQA2/DQB2 complex. **Therapeutic Potential:** The highly restricted expression of the HLA-DQA2/DQB2 complex on the surface of [Langerhans cell](/details-cell/CL0000453)s and a subset of dendritic cells makes it an attractive therapeutic target. This specificity could be leveraged to selectively modulate immune responses in tissues like the skin. For inflammatory skin conditions such as psoriasis or atopic dermatitis, where Langerhans cells play a pathogenic role, an antibody-drug conjugate targeting this complex could deliver immunosuppressive agents directly to these cells, minimizing systemic side effects. Conversely, in the context of cutaneous melanoma, an antibody targeting HLA-DQA2/DQB2 could deliver an adjuvant or immunostimulatory payload to enhance local antigen presentation and promote an anti-tumor T cell response. Therefore, it represents a promising target for cell-specific immunomodulation.

Genular Protein ID: 817666625

Symbol: DQB2_HUMAN

Name: HLA class II histocompatibility antigen, DQ beta 2 chain

UniProtKB Accession Codes:

P05538 A6NIA5 Q29826 Q29870 Q29871 Q29872 Q29873 Q5SR06

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 14 Ensembl 8 ExpressionAtlas 1 GO 20 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 9 KEGG 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 2 PRO 1 PROSITE 2 PathwayCommons 1 PeptideAtlas 1 Pfam 2 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 7 RefSeq 1 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 3036828

Title: Class II genes of the human major histocompatibility complex. Comparisons of the DQ and DX alpha and beta genes.

PubMed ID: 3036828

DOI: 10.1016/s0021-9258(18)47482-0

PubMed ID: 8568858

Title: Evolutionary dynamics of non-coding sequences within the class II region of the human MHC.

PubMed ID: 8568858

DOI: 10.1006/jmbi.1996.0001

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 3858830

Title: Gene organization of DC and DX subregions of the human major histocompatibility complex.

PubMed ID: 3858830

DOI: 10.1073/pnas.82.10.3410

PubMed ID: 2564844

Title: Remarkable sequence conservation of the HLA-DQB2 locus (DX beta) within the highly polymorphic DQ subregion of the human MHC.

PubMed ID: 2564844

DOI: 10.1007/bf00717908

PubMed ID: 9036956

Title: The nonpolymorphic MHC class II isotype, HLA-DQA2, is expressed on the surface of B lymphoblastoid cells.

PubMed ID: 9036956

PubMed ID: 11334674

Title: Absence of in vivo DNA-protein interactions in the DQA2 and DQB2 promoter regions.

PubMed ID: 11334674

DOI: 10.1016/s0198-8859(01)00236-1

PubMed ID: 8598037

Title: Invariant chain structure and MHC class II function.

PubMed ID: 8598037

DOI: 10.1016/s0092-8674(00)81025-9

PubMed ID: 11684289

Title: Presentation of antigens by MHC class II molecules: getting the most out of them.

PubMed ID: 11684289

DOI: 10.1016/s0161-5890(01)00069-4

PubMed ID: 18046453

Title: MHC class II molecules on the move for successful antigen presentation.

PubMed ID: 18046453

DOI: 10.1038/sj.emboj.7601945

PubMed ID: 17241953

Title: Autophagy in MHC class II presentation: sampling from within.

PubMed ID: 17241953

DOI: 10.1016/j.immuni.2007.01.005

PubMed ID: 19092054

Title: MHC class II transport at a glance.

PubMed ID: 19092054

DOI: 10.1242/jcs.035089

PubMed ID: 19533806

Title: CD74 in antigen presentation, inflammation, and cancers of the gastrointestinal tract.

PubMed ID: 19533806

DOI: 10.3748/wjg.15.2855

PubMed ID: 22407913

Title: HLA-DQA2 and HLA-DQB2 genes are specifically expressed in human Langerhans cells and encode a new HLA class II molecule.

PubMed ID: 22407913

DOI: 10.4049/jimmunol.1103048

Sequence Information:

  • Length: 268
  • Mass: 30387
  • Checksum: 2746ED6CC5D44AF2
  • Sequence:
    • MSWKMALQIP GGFWAAAVTV MLVMLSTPVA EARDFPKDFL VQFKGMCYFT NGTERVRGVA 
RYIYNREEYG RFDSDVGEFQ AVTELGRSIE DWNNYKDFLE QERAAVDKVC RHNYEAELRT 
TLQRQVEPTV TISPSRTEAL NHHNLLVCSV TDFYPAQIKV RWFRNDQEET AGVVSTSLIR 
NGDWTFQILV MLEITPQRGD IYTCQVEHPS LQSPITVEWR AQSESAQSKM LSGIGGFVLG 
LIFLGLGLII RHRGQKGPRG PPPAGLLH

Genular Protein ID: 1080849774

Symbol: Q5SR05_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q5SR05

Database IDs:

ARBA 11 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 1 Ensembl 5 GO 5 Gene3D 1 GeneTree 1 HGNC 1 HOGENOM 1 InterPro 9 MANE-Select 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 3 PeptideAtlas 1 Pfam 2 Proteomes 2 ProteomicsDB 2 RefSeq 1 SAM 2 SMART 2 SUPFAM 2 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 264
  • Mass: 29854
  • Checksum: 26E9B8B769A9D55A
  • Sequence:
    • MALQIPGGFW AAAVTVMLVM LSTPVAEARD FPKDFLVQFK GMCYFTNGTE RVRGVARYIY 
NREEYGRFDS DVGEFQAVTE LGRSIEDWNN YKDFLEQERA AVDKVCRHNY EAELRTTLQR 
QVEPTVTISP SRTEALNHHN LLVCSVTDFY PAQIKVRWFR NDQEETAGVV STSLIRNGDW 
TFQILVMLEI TPQRGDIYTC QVEHPSLQSP ITVEWRAQSE SAQSKMLSGI GGFVLGLIFL 
GLGLIIRHRG QKGPRGPPPA GLLH

Genular Protein ID: 2918179020

Symbol: A0A2H4Z4R5_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A2H4Z4R5

Database IDs:

ARBA 11 AlphaFoldDB 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 15 GO 5 Gene3D 1 InterPro 9 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 3 Pfam 2 RefSeq 1 SAM 1 SMART 2 SUPFAM 2

Sequence Information:

  • Length: 219
  • Mass: 25302
  • Checksum: 76F9BEF894C6AAED
  • Sequence:
    • MALQIPGGFW AAAVTVMLVM LSTPVAEARD FPKDFLVQFK GMCYFTNGTE RVRGVARYIY 
NREEYGRFDS DVGEFQAVTE LGRSIEDWNN YKDFLEQERA AVDKVCRHNY EAELRTTLQR 
QVEPTVTISP SRTEALNHHN LLVCSVTDFY PAQIKVRWFR NDQEETAGVV STSLIRNGDW 
TFQILVMLEI TPQRGDIYTC QVEHPSLQSP ITVEWRLLH

Genular Protein ID: 807657653

Symbol: A2ADX3_HUMAN

Name: N/A

UniProtKB Accession Codes:

A2ADX3

Database IDs:

ARBA 11 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 5 GO 5 Gene3D 1 GeneTree 1 HGNC 1 InterPro 9 NCBI Taxonomy 1 OMA 1 OrthoDB 1 PANTHER 2 PROSITE 3 PeptideAtlas 1 Pfam 2 Proteomes 2 ProteomicsDB 2 RefSeq 1 SAM 3 SMART 2 SUPFAM 2 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

Sequence Information:

  • Length: 275
  • Mass: 30948
  • Checksum: 6E1A385D96839EE0
  • Sequence:
    • MALQIPGGFW AAAVTVMLVM LSTPVAEARD FPKDFLVQFK GMCYFTNGTE RVRGVARYIY 
NREEYGRFDS DVGEFQAVTE LGRSIEDWNN YKDFLEQERA AVDKVCRHNY EAELRTTLQR 
QVEPTVTISP SRTEALNHHN LLVCSVTDFY PAQIKVRWFR NDQEETAGVV STSLIRNGDW 
TFQILVMLEI TPQRGDIYTC QVEHPSLQSP ITVEWRAQSE SAQSKMLSGI GGFVLGLIFL 
GLGLIIRHRG QKGPRGPPPA GNISAMIQSG ERAQA