Details for: CD8B

Gene ID: 926

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: CD8B

Ensembl ID: ENSG00000172116

Description: CD8 subunit beta

Cell Significance Landscape

Associated with

Significant Cells

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

  • naive thymus-derived CD8-positive, alpha-beta T cell CL0000900
    CSI 74.5
    rCSI 52.32%
    PRS 99.95
  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 62.81
    rCSI 42.31%
    PRS 100
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 54.44
    rCSI 55.48%
    PRS 99.61
  • alpha-beta T cell CL0000789
    CSI 35.72
    rCSI 41.85%
    PRS 99.94
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 27.94
    rCSI 21.25%
    PRS 99.98
  • CD8-positive, alpha-beta memory T cell CL0000909
    CSI 27.54
    rCSI 28.76%
    PRS 99.89
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 24.75
    rCSI 29.99%
    PRS 94.94
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 23
    rCSI 39.34%
    PRS 99.84
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 21.8
    rCSI 43.45%
    PRS 99.84
  • mature T cell CL0002419
    CSI 20.68
    rCSI 16.08%
    PRS 100
  • activated CD8-positive, alpha-beta T cell CL0000906
    CSI 19.83
    rCSI 19.49%
    PRS 99.95
  • double negative thymocyte CL0002489
    CSI 19.39
    rCSI 13.48%
    PRS 99.94
  • mononuclear phagocyte CL0000113
    CSI 19.34
    rCSI 42.58%
    PRS 99.91
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 16.98
    rCSI 15.46%
    PRS 99.95
  • naive T cell CL0000898
    CSI 15.31
    rCSI 10.66%
    PRS 100
  • platelet CL0000233
    CSI 12.67
    rCSI 52.58%
    PRS 98.54
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 11.91
    rCSI 14.22%
    PRS 99.83
  • CD8-positive, alpha-beta thymocyte CL0000811
    CSI 11.57
    rCSI 18.05%
    PRS 98.96
  • memory T cell CL0000813
    CSI 9.9
    rCSI 19.06%
    PRS 99.96
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 9.42
    rCSI 27.01%
    PRS 100
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 7.69
    rCSI 38.6%
    PRS 99.94
  • natural T-regulatory cell CL0000903
    CSI 7.57
    rCSI 14.33%
    PRS 99.95
  • melanocyte of skin CL1000458
    CSI 5.85
    rCSI 7.97%
    PRS 94.62
  • thymocyte CL0000893
    CSI 5.49
    rCSI 19.5%
    PRS 99.83
  • exhausted T cell CL0011025
    CSI 4.44
    rCSI 75.18%
    PRS 99.09
  • lung resident memory CD8-positive, alpha-beta T cell CL4033039
    CSI 3.77
    rCSI 9.75%
    PRS 100
  • lung resident memory CD4-positive, alpha-beta T cell CL4033038
    CSI 2.9
    rCSI 28.56%
    PRS 100
  • activated CD4-positive, alpha-beta T cell, human CL0001043
    CSI 2.68
    rCSI 6.44%
    PRS 100
  • cytotoxic T cell CL0000910
    CSI 1.35
    rCSI 7.72%
    PRS 98.46
  • double negative T regulatory cell CL0011024
    CSI 1.24
    rCSI 23.51%
    PRS 100

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.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
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    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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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 [CD8B](/details-gene/926) encodes the CD8 subunit beta, a T-cell surface glycoprotein that is a critical component of the T-cell receptor (TCR) complex. It forms a heterodimer with the CD8 alpha chain ([CD8A](/details-gene/925)), creating the CD8 coreceptor essential for the recognition of MHC class I molecules presented by antigen-presenting cells. This interaction is fundamental for the activation and function of cytotoxic T lymphocytes. The expression of [CD8B](/details-gene/926) is highly restricted to the T cell lineage, serving as a canonical marker for various subsets of CD8-positive T cells, from their development in the thymus to their differentiation into effector and memory cells. Its clinical relevance is noted under OMIM [186730](https://omim.org/entry/186730). ## Cellular Roles and Expression Landscape The expression profile of [CD8B](/details-gene/926) definitively establishes it as a key molecule in the adaptive immune system, with its significance overwhelmingly concentrated in the T lymphocyte lineage. **Overall**, the gene shows the highest significance in cells central to cytotoxic T cell development and function. It is a top marker for the [naive thymus-derived CD8-positive, alpha-beta T cell](/details-cell/CL0000900) (CSI: 74.50), highlighting its role in mature T cells poised for an immune response. Its high significance continues in memory populations, including the [central memory CD8-positive, alpha-beta T cell](/details-cell/CL0000907) (CSI: 62.81) and various other memory subsets, underscoring its stable expression and importance throughout the lifespan of a cytotoxic T cell. Furthermore, its prominence in thymic precursors, such as the [double-positive, alpha-beta thymocyte](/details-cell/CL0000809) (CSI: 54.44), confirms its fundamental role during T cell selection and maturation. This highly specific expression pattern across the T cell differentiation spectrum suggests [CD8B](/details-gene/926) is not merely a passive marker but an integral functional component required for the identity and activity of these cells. Research confirms that the beta chain is essential for efficient coreceptor function, coupling the TCR to downstream signaling complexes [Link](https://doi.org/10.1084/jem.194.10.1485). ## Pathways and Molecular Function The molecular functions and pathway involvements of [CD8B](/details-gene/926) are tightly aligned with its role as a T cell coreceptor. Gene Ontology annotations classify its molecular function with terms such as `Coreceptor activity` ([GO:0015026](https://www.ebi.ac.uk/QuickGO/term/GO:0015026)) and `Mhc class i protein binding` ([GO:0042288](https://www.ebi.ac.uk/QuickGO/term/GO:0042288)). These functions are executed at the `Cell surface` ([GO:0009986](https://www.ebi.ac.uk/QuickGO/term/GO:0009986)) as part of the `T cell receptor complex` ([GO:0042101](https://www.ebi.ac.uk/QuickGO/term/GO:0042101)). These activities are central to the biological processes of `T cell activation` ([GO:0042110](https://www.ebi.ac.uk/QuickGO/term/GO:0042110)) and the broader `Adaptive immune response` ([GO:0002250](https://www.ebi.ac.uk/QuickGO/term/GO:0002250)). Consistent with these functions, Reactome pathway analysis places [CD8B](/details-gene/926) in the core `Adaptive immune system` pathway ([R-HSA-1280218](https://reactome.org/content/detail/R-HSA-1280218)) and more specifically in `Immunoregulatory interactions between a lymphoid and a non-lymphoid cell` ([R-HSA-198933](https://reactome.org/content/detail/R-HSA-198933)). Notably, it is also implicated in pathways related to viral pathogenesis, such as `Hiv infection` ([R-HSA-162906](https://reactome.org/content/detail/R-HSA-162906)) and `Nef mediated cd8 down-regulation` ([R-HSA-182218](https://reactome.org/content/detail/R-HSA-182218)), highlighting the CD8 complex as a key target for viral immune evasion strategies. ## Research Directions While [CD8B](/details-gene/926) is well-established as a core component of the CD8 complex, its specific contribution relative to the CD8A homodimer and its role in disease pathogenesis present avenues for further research. **Proposed Hypotheses:** 1. The ratio of CD8A/CD8B heterodimers to CD8A/CD8A homodimers on the cell surface is dynamically regulated during T cell differentiation from naive to effector and memory states. This differential expression may fine-tune TCR signaling thresholds, influencing cell fate decisions and the functional potency of memory T cell recall responses. 2. Genetic variants within the [CD8B](/details-gene/926) locus may alter its interaction with the HIV-1 Nef protein, thereby influencing the efficiency of CD8 downregulation and contributing to observed variations in viral load and disease progression rates among individuals. **Experimental Approach:** To test the first hypothesis regarding the dynamic regulation of CD8 heterodimers, one could employ a combination of quantitative flow cytometry and super-resolution microscopy. Primary human T cells could be sorted into naive, central memory, effector memory, and terminal effector subsets based on established surface markers. Using antibodies specific for [CD8A](/details-gene/925) and [CD8B](/details-gene/926), quantitative flow cytometry would determine the total surface expression of each subunit. Subsequently, a technique like Stochastic Optical Reconstruction Microscopy (STORM) or DNA-PAINT could be used to visualize and quantify the colocalization of CD8A and CD8B at the single-molecule level on the plasma membrane of these T cell subsets, providing direct evidence for changes in the abundance of heterodimers versus homodimers. **Therapeutic Potential:** Given its highly specific expression on CD8-positive T cells, [CD8B](/details-gene/926) is an excellent candidate for therapeutic targeting, not for modulating its function, but for cell-specific delivery or depletion. In autoimmune diseases or graft-versus-host disease mediated by pathogenic CD8+ T cells, [CD8B](/details-gene/926) could be targeted with depleting monoclonal antibodies or antibody-drug conjugates to specifically eliminate these disease-driving cells while sparing other immune populations. This approach would represent a targeted inhibition strategy aimed at a specific cellular population rather than a molecular pathway.

Genular Protein ID: 2767409943

Symbol: CD8B_HUMAN

Name: T-cell surface glycoprotein CD8 beta chain

UniProtKB Accession Codes:

P10966 P14860 P14861 Q15980 Q496E0 Q496E1 Q496E2 Q9UDB4 Q9UDB5 Q9UDB6 Q9UDB7 Q9UDB8 Q9UDB9 Q9UDC0 Q9UQ55

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 5 CDD 1 CTD 1 ComplexPortal 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 37 Ensembl 5 ExpressionAtlas 1 GO 13 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 8 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 9 RNAct 1 Reactome 2 RefSeq 5 SMART 2 SMR 1 SUPFAM 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 3145195

Title: A second subunit of CD8 is expressed in human T cells.

PubMed ID: 3145195

DOI: 10.1002/j.1460-2075.1988.tb03217.x

PubMed ID: 3145196

Title: The human Lyt-3 molecule requires CD8 for cell surface expression.

PubMed ID: 3145196

DOI: 10.1002/j.1460-2075.1988.tb03221.x

PubMed ID: 3264320

Title: A second chain of human CD8 is expressed on peripheral blood lymphocytes.

PubMed ID: 3264320

DOI: 10.1084/jem.168.6.1993

PubMed ID: 1541829

Title: Recent duplication of the two human CD8 beta-chain genes.

PubMed ID: 1541829

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

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: 8436166

Title: Transcriptional diversity at the duplicated human CD8 beta loci.

PubMed ID: 8436166

DOI: 10.1002/eji.1830230203

PubMed ID: 10925291

Title: Essential role of CD8 palmitoylation in CD8 coreceptor function.

PubMed ID: 10925291

DOI: 10.4049/jimmunol.165.4.2068

PubMed ID: 11714755

Title: CD8beta endows CD8 with efficient coreceptor function by coupling T cell receptor/CD3 to raft-associated CD8/p56(lck) complexes.

PubMed ID: 11714755

DOI: 10.1084/jem.194.10.1485

PubMed ID: 17145893

Title: Influence of human CD8 on antigen recognition by T-cell receptor-transduced cells.

PubMed ID: 17145893

DOI: 10.1158/0008-5472.can-06-2379

Sequence Information:

  • Length: 210
  • Mass: 23722
  • Checksum: 675AD919585F4B80
  • Sequence:
    • MRPRLWLLLA AQLTVLHGNS VLQQTPAYIK VQTNKMVMLS CEAKISLSNM RIYWLRQRQA 
PSSDSHHEFL ALWDSAKGTI HGEEVEQEKI AVFRDASRFI LNLTSVKPED SGIYFCMIVG 
SPELTFGKGT QLSVVDFLPT TAQPTKKSTL KKRVCRLPRP ETQKGPLCSP ITLGLLVAGV 
LVLLVSLGVA IHLCCRRRRA RLRFMKQFYK

Genular Protein ID: 933438988

Symbol: Q53QL8_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q53QL8

Database IDs:

ARBA 7 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 5 Gene3D 1 InterPro 6 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 Pfam 1 RefSeq 1 SAM 2 SMART 2 SMR 1 SUPFAM 1

Sequence Information:

  • Length: 246
  • Mass: 27699
  • Checksum: 348BD12A23CE59CD
  • Sequence:
    • MRPRLWLLLA AQLTVLHGNS VLQQTPAYIK VQTNKMVMLS CEAKISLSNM RIYWLRQRQA 
PSSDSHHEFL ALWDSAKGTI HGEEVEQEKI AVFRDASRFI LNLTSVKPED SGIYFCMIVG 
SPELTFGKGT QLSVVDFLPT TAQPTKKSTL KKRVCRLPRP ETQKGPLCSP ITLGLLVAGV 
LVLLVSLGVA IHLCCRRRRA RLRFMKQKFN IVCLKISGFT TCCCFQILQM SREYGFGVLL 
QKDIGQ