Details for: CD8A

Gene ID: 925

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: CD8A

Ensembl ID: ENSG00000153563

Description: CD8 subunit alpha

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • central memory CD8-positive, alpha-beta T cell CL0000907
    CSI 84.6
    rCSI 57%
    PRS 97.56
  • CD8-positive, alpha-beta memory T cell CL0000909
    CSI 59.88
    rCSI 62.54%
    PRS 95.93
  • double-positive, alpha-beta thymocyte CL0000809
    CSI 54.24
    rCSI 55.28%
    PRS 94.99
  • alpha-beta T cell CL0000789
    CSI 47.9
    rCSI 56.13%
    PRS 97.08
  • activated CD8-positive, alpha-beta T cell, human CL0001049
    CSI 41
    rCSI 70.14%
    PRS 96.01
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 35.88
    rCSI 43.47%
    PRS 71.15
  • effector CD8-positive, alpha-beta T cell CL0001050
    CSI 33.43
    rCSI 25.43%
    PRS 97.69
  • mucosal invariant T cell CL0000940
    CSI 33.35
    rCSI 26.95%
    PRS 95
  • mature T cell CL0002419
    CSI 32.88
    rCSI 25.58%
    PRS 97.12
  • CD8-positive, CD28-negative, alpha-beta regulatory T cell CL0000920
    CSI 32.11
    rCSI 64.02%
    PRS 96.45
  • CD16-positive, CD56-dim natural killer cell, human CL0000939
    CSI 29.52
    rCSI 19.67%
    PRS 95.58
  • naive thymus-derived CD8-positive, alpha-beta T cell CL0000900
    CSI 27.92
    rCSI 19.61%
    PRS 96.41
  • effector memory CD8-positive, alpha-beta T cell CL0000913
    CSI 26.8
    rCSI 24.41%
    PRS 97.05
  • double negative thymocyte CL0002489
    CSI 25.8
    rCSI 17.94%
    PRS 97.1
  • activated CD8-positive, alpha-beta T cell CL0000906
    CSI 21.72
    rCSI 21.35%
    PRS 96.48
  • CD4-positive, alpha-beta thymocyte CL0000810
    CSI 21.42
    rCSI 17.16%
    PRS 95.12
  • mononuclear phagocyte CL0000113
    CSI 20.33
    rCSI 44.74%
    PRS 92.43
  • activated CD4-positive, alpha-beta T cell CL0000896
    CSI 20.27
    rCSI 18.74%
    PRS 97.54
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 18.32
    rCSI 13.15%
    PRS 97.61
  • CD8-positive, alpha-beta cytotoxic T cell CL0000794
    CSI 17.17
    rCSI 20.5%
    PRS 97.46
  • CD8-positive, alpha-beta thymocyte CL0000811
    CSI 16.63
    rCSI 25.94%
    PRS 96.66
  • T-helper 17 cell CL0000899
    CSI 15.84
    rCSI 12.58%
    PRS 98
  • platelet CL0000233
    CSI 13.11
    rCSI 54.38%
    PRS 86.78
  • natural T-regulatory cell CL0000903
    CSI 12.56
    rCSI 23.78%
    PRS 98.28
  • activated type II NK T cell CL0000931
    CSI 12.45
    rCSI 14.01%
    PRS 96.85
  • memory T cell CL0000813
    CSI 12.26
    rCSI 23.62%
    PRS 97.75
  • effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062
    CSI 11.79
    rCSI 59.14%
    PRS 96.82
  • erythrocyte CL0000232
    CSI 11.34
    rCSI 25.72%
    PRS 88.57
  • thymocyte CL0000893
    CSI 9.44
    rCSI 33.54%
    PRS 98.08
  • effector CD4-positive, alpha-beta T cell CL0001044
    CSI 8.67
    rCSI 24.87%
    PRS 98.37
  • CD8-alpha-alpha-positive, alpha-beta intraepithelial T cell CL0000915
    CSI 7.71
    rCSI 35.06%
    PRS 97.15
  • intraepithelial lymphocyte CL0002496
    CSI 6.51
    rCSI 17.71%
    PRS 97.26
  • exhausted T cell CL0011025
    CSI 5.78
    rCSI 97.79%
    PRS 93.4
  • hepatic pit cell CL2000054
    CSI 4.4
    rCSI 60.29%
    PRS 95.42
  • lung resident memory CD8-positive, alpha-beta T cell CL4033039
    CSI 4.23
    rCSI 10.95%
    PRS 97.6
  • helper T cell CL0000912
    CSI 3.6
    rCSI 5.09%
    PRS 86.34
  • cytotoxic T cell CL0000910
    CSI 2.18
    rCSI 12.49%
    PRS 89.52
  • group 3 innate lymphoid cell CL0001071
    CSI 1.94
    rCSI 1.46%
    PRS 93.43
  • lung resident memory CD4-positive, alpha-beta T cell CL4033038
    CSI 1.62
    rCSI 15.96%
    PRS 96.5
  • activated CD4-positive, alpha-beta T cell, human CL0001043
    CSI 1.34
    rCSI 3.22%
    PRS 97.87
  • innate lymphoid cell CL0001065
    CSI 1.24
    rCSI 2.56%
    PRS 84.76

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):
    • 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)

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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 [CD8A](/details-gene/925) encodes the alpha chain of the CD8 surface glycoprotein, a key co-receptor for the T-cell receptor (TCR) complex. It primarily functions by binding to MHC class I molecules, stabilizing the TCR-MHC interaction and facilitating the activation of cytotoxic T cells and other immune cell subsets. As a canonical marker for cytotoxic T lymphocytes, its expression is tightly linked to the cellular machinery of the adaptive immune system, particularly in processes involving T cell development, activation, and cell-mediated immunity. Mutations or alterations in its function are associated with immunodeficiency ([186910](https://omim.org/entry/186910)). ## Cellular Roles and Expression Landscape The expression profile of [CD8A](/details-gene/925) unequivocally establishes its role as a cornerstone of the T cell lineage. **Overall**, the gene shows the highest significance in mature, antigen-experienced T cell subsets, with the top score observed in [central memory CD8-positive, alpha-beta T cell](/details-cell/CL0000907) (CSI: 84.60), followed by other memory and activated T cell populations such as [CD8-positive, alpha-beta memory T cell](/details-cell/CL0000909) and [activated CD8-positive, alpha-beta T cell, human](/details-cell/CL0001049). This high-level expression underscores its crucial function not only in effector responses but also in the maintenance of long-term immunological memory. The gene's importance spans the entire T cell life cycle, as evidenced by its significant expression during T cell development in [double-positive, alpha-beta thymocyte](/details-cell/CL0000809) and [double negative thymocyte](/details-cell/CL0002489), and in antigen-naive populations like [naive thymus-derived CD8-positive, alpha-beta T cell](/details-cell/CL0000900). Beyond conventional T cells, [CD8A](/details-gene/925) is also a significant marker for unconventional T cells, such as [mucosal invariant T cell](/details-cell/CL0000940), suggesting a broader role in immune surveillance. Notably, its expression is also found on a subset of innate immune cells, specifically [CD16-positive, CD56-dim natural killer cell, human](/details-cell/CL0000939), where it may participate in regulating cytolytic activity, a function distinct from its co-receptor role in T cells [Link](https://doi.org/10.1111/j.1365-2567.2005.02235.x). The collective expression pattern highlights [CD8A](/details-gene/925) as a defining molecule for cell-mediated cytotoxic immunity. ## Pathways and Molecular Function Functionally, [CD8A](/details-gene/925) is integral to the initiation of adaptive immune responses. Its molecular function is dominated by its '[Coreceptor activity](/details-go/GO:0015026)' and specific binding to '[Mhc class i protein complex binding](/details-go/GO:0023024)', as described in early structural studies [Link](https://doi.org/10.1038/338345a0). This interaction is a critical checkpoint in the '[T cell receptor signaling pathway](/details-go/GO:0050852)', which ultimately leads to '[T cell activation](/details-go/GO:0042110)' and '[cytotoxic t cell differentiation](/details-go/GO:0045065)'. These molecular events are consistent with its high expression in T cells and its central role in the broader '[Adaptive immune system](/details-reactome/R-HSA-1280218)' pathway. As a component of the '[T cell receptor complex](/details-go/GO:0042101)' located on the '[external side of plasma membrane](/details-go/GO:0009897)', [CD8A](/details-gene/925) is perfectly positioned to execute its role in '[Immunoregulatory interactions between a lymphoid and a non-lymphoid cell](/details-reactome/R-HSA-198933)', facilitating the recognition of pathogen-infected or malignant cells by the immune system. The existence of alternatively spliced, secreted forms of the protein suggests additional, potentially soluble, immunoregulatory functions [Link](https://doi.org/10.1073/pnas.86.3.998). ## Research Directions While the role of [CD8A](/details-gene/925) in conventional T cells is well-established, its function in unconventional T cells and innate lymphocytes remains an area of active investigation. The data suggests several testable hypotheses. 1. **Hypothesis 1:** In [mucosal invariant T cells](/details-cell/CL0000940) (MAIT cells), which recognize microbial vitamin B metabolites presented by the MHC-I-like molecule MR1, [CD8A](/details-gene/925) may function as a co-receptor that stabilizes the MR1-TCR interaction, thereby lowering the activation threshold and enhancing the speed and sensitivity of the anti-microbial response. 2. **Hypothesis 2:** The expression of [CD8A](/details-gene/925) homodimers on [CD16-positive, CD56-dim natural killer cells](/details-cell/CL0000939) serves to modulate their cytolytic activity upon binding to non-classical MHC-I molecules (e.g., HLA-E) on target cells. This interaction may either inhibit NK cell function to prevent auto-reactivity or, conversely, act as a co-stimulatory signal to enhance killing of stressed or virally infected cells. * **Proposed Experiment for Hypothesis 2:** To elucidate the role of [CD8A](/details-gene/925) on [NK cells](/details-cell/CL0000939), one could use CRISPR-Cas9 to knock out [CD8A](/details-gene/925) in a human NK cell line (e.g., NK-92) or in primary human [NK cells](/details-cell/CL0000939). The cytotoxic capacity of these [CD8A](/details-gene/925)-deficient cells could then be compared to wild-type controls in co-culture assays against target cell lines engineered to express specific classical and non-classical MHC-I ligands. Changes in degranulation (CD107a expression), cytokine production (IFN-gamma), and target cell lysis would reveal the functional consequence of [CD8A](/details-gene/925) engagement on [NK cells](/details-cell/CL0000939). * **Therapeutic Potential:** [CD8A](/details-gene/925) itself is not typically a direct therapeutic target for inhibition, as this would suppress critical anti-tumor and anti-viral immunity. Instead, its immense therapeutic value lies in its utility as a biomarker and a tool for cell-based therapies. It is the defining marker used to isolate and enrich cytotoxic T lymphocytes for adoptive cell transfer, including CAR-T cell manufacturing. Monitoring the abundance of [CD8-positive T cells](/details-cell/CL0000624) in tumors is a key prognostic and predictive biomarker for responses to immune checkpoint inhibitors. Therefore, strategies that enhance the function or expansion of the cells marked by [CD8A](/details-gene/925) represent the primary therapeutic application.

Genular Protein ID: 872863526

Symbol: CD8A_HUMAN

Name: T-cell surface glycoprotein CD8 alpha chain

UniProtKB Accession Codes:

P01732 B4DT80 D6W5M8 Q13970 Q4ZG17

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CDD 1 CORUM 1 CPTC 1 CTD 1 ChiTaRS 1 ComplexPortal 2 DMDM 1 DNASU 1 DisGeNET 1 EMBL 15 Ensembl 4 EvolutionaryTrace 1 ExpressionAtlas 1 GO 18 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 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 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 8 PDBsum 8 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 3 RNAct 1 Reactome 1 RefSeq 3 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 3871356

Title: The isolation and sequence of the gene encoding T8: a molecule defining functional classes of T lymphocytes.

PubMed ID: 3871356

DOI: 10.1016/0092-8674(85)90138-2

PubMed ID: 3936473

Title: Structure of Leu-2/T8 as deduced from the sequence of a cDNA clone.

PubMed ID: 3936473

PubMed ID: 3918796

Title: The T cell differentiation antigen Leu-2/T8 is homologous to immunoglobulin and T cell receptor variable regions.

PubMed ID: 3918796

DOI: 10.1016/0092-8674(85)90207-7

PubMed ID: 2509342

Title: Structure and expression of the gene encoding CD8 alpha chain (Leu-2/T8).

PubMed ID: 2509342

DOI: 10.1007/bf02425282

PubMed ID: 2496167

Title: Alternatively spliced mRNA encodes a secreted form of human CD8 alpha. Characterization of the human CD8 alpha gene.

PubMed ID: 2496167

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 2536941

Title: A secreted form of the human lymphocyte cell surface molecule CD8 arises from alternative splicing.

PubMed ID: 2536941

DOI: 10.1073/pnas.86.3.998

PubMed ID: 6605969

Title: The T8 antigen is a multimeric complex of two distinct subunits on human thymocytes but consists of homomultimeric forms on peripheral blood T lymphocytes.

PubMed ID: 6605969

DOI: 10.1016/s0021-9258(17)43915-9

PubMed ID: 2512251

Title: Phosphorylation and down-regulation of CD4 and CD8 in human CTLs and mouse L cells.

PubMed ID: 2512251

DOI: 10.1007/bf02421181

PubMed ID: 2784196

Title: Polymorphism in the alpha 3 domain of HLA-A molecules affects binding to CD8.

PubMed ID: 2784196

DOI: 10.1038/338345a0

PubMed ID: 1460019

Title: Post-translational processing of an O-glycosylated protein, the human CD8 glycoprotein, during the intracellular transport to the plasma membrane.

PubMed ID: 1460019

DOI: 10.1016/s0021-9258(19)74024-1

PubMed ID: 7923932

Title: A distinctive form of soluble CD8 is secreted by stimulated CD8+ cells in HIV-1-infected and high-risk individuals.

PubMed ID: 7923932

DOI: 10.1006/clin.1994.1195

PubMed ID: 12853576

Title: Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G.

PubMed ID: 12853576

DOI: 10.1073/pnas.1431057100

PubMed ID: 16236125

Title: Ligation of CD8alpha on human natural killer cells prevents activation-induced apoptosis and enhances cytolytic activity.

PubMed ID: 16236125

DOI: 10.1111/j.1365-2567.2005.02235.x

PubMed ID: 17678538

Title: CD8 alpha is expressed by human monocytes and enhances Fc gamma R-dependent responses.

PubMed ID: 17678538

DOI: 10.1186/1471-2172-8-12

PubMed ID: 17341584

Title: CD8 Raft localization is induced by its assembly into CD8alpha beta heterodimers, Not CD8alpha alpha homodimers.

PubMed ID: 17341584

DOI: 10.1074/jbc.m701027200

PubMed ID: 23657257

Title: Immune surveillance by CD8alphaalpha+ skin-resident T cells in human herpes virus infection.

PubMed ID: 23657257

DOI: 10.1038/nature12110

PubMed ID: 26082771

Title: A subset of human plasmacytoid dendritic cells expresses CD8alpha upon exposure to herpes simplex virus type 1.

PubMed ID: 26082771

DOI: 10.3389/fmicb.2015.00557

PubMed ID: 1547508

Title: Crystal structure of a soluble form of the human T cell coreceptor CD8 at 2.6-A resolution.

PubMed ID: 1547508

DOI: 10.1016/0092-8674(92)90085-q

PubMed ID: 9177355

Title: Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2.

PubMed ID: 9177355

DOI: 10.1038/42523

PubMed ID: 14500983

Title: A zinc clasp structure tethers Lck to T cell coreceptors CD4 and CD8.

PubMed ID: 14500983

DOI: 10.1126/science.1085643

PubMed ID: 11435463

Title: Familial CD8 deficiency due to a mutation in the CD8 alpha gene.

PubMed ID: 11435463

DOI: 10.1172/jci10993

PubMed ID: 17658607

Title: Gly111Ser mutation in CD8A gene causing CD8 immunodeficiency is found in Spanish Gypsies.

PubMed ID: 17658607

DOI: 10.1016/j.molimm.2007.05.022

Sequence Information:

  • Length: 235
  • Mass: 25729
  • Checksum: FCCA29BAA73726BB
  • Sequence:
    • MALPVTALLL PLALLLHAAR PSQFRVSPLD RTWNLGETVE LKCQVLLSNP TSGCSWLFQP 
RGAAASPTFL LYLSQNKPKA AEGLDTQRFS GKRLGDTFVL TLSDFRRENE GYYFCSALSN 
SIMYFSHFVP VFLPAKPTTT PAPRPPTPAP TIASQPLSLR PEACRPAAGG AVHTRGLDFA 
CDIYIWAPLA GTCGVLLLSL VITLYCNHRN RRRVCKCPRP VVKSGDKPSL SARYV

Genular Protein ID: 3883293718

Symbol: Q8TAW8_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q8TAW8

Database IDs:

ARBA 7 AlphaFoldDB 1 BioGRID-ORCS 1 CDD 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 2 GO 4 Gene3D 1 InterPro 6 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PROSITE 2 PeptideAtlas 1 Pfam 1 PharmGKB 1 RefSeq 3 SAM 2 SMART 2 SMR 1 SUPFAM 1

Citations:

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

Sequence Information:

  • Length: 235
  • Mass: 25669
  • Checksum: FCDFC9B5472D26BB
  • Sequence:
    • MALPVTALLL PLALLLHAAR PSQFRVSPLD RTWNLGETVE LKCQVLLSNP TSGCSWLFQP 
RGAAASPTFL LYLSQNKPKA AEGLDTQRFS GKRLGDTFVL TLSDFRRENE GCYFCSALSN 
SIMYFSHFVP VFLPAKPTTT PAPRPPTPAP TIASQPLSLR PEACRPAAGG AVHTRGLDFA 
CDIYIWAPLA GTCGVLLLSL VITLYCNHRN RRRVCKCPRP VVKSGDKPSL SARYV

Genular Protein ID: 3569746370

Symbol: Q6ZVS2_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q6ZVS2

Database IDs:

ARBA 6 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 DNASU 1 DisGeNET 1 EMBL 2 GO 4 Gene3D 1 InterPro 4 KEGG 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 2 PharmGKB 1 RefSeq 2 SAM 2 SUPFAM 1

Sequence Information:

  • Length: 152
  • Mass: 16713
  • Checksum: 6911F40F86122E02
  • Sequence:
    • MRNQAPGRPK GATFPPRRPT GSRAPPLAPE LRAKQRPGER VMALPVTALL LPLALLLHAA 
RPSQFRVSPL DRTWNLGETV ELKCQVLLSN PTSGCSWLFQ PRGAAASPTF LLYLSQNKPK 
AAEGLDTQRF SGKRLGDTFV LTLSDFRREN EG