Details for: CL0001049

Cell ID: CL0001049

Cell Name: activated CD8-positive, alpha-beta T cell, human

Description: This cell type is compatible with the HIPC Lyoplate markers for 'activated CD8+ T cell', but includes via logical inference from its parent additional markers known to be expressed on activated CD8+ T cells. The inclusion of HLA-DRA in the definition restricts this definition to human activated CD8+ T cells, as activated mouse T cells do not express MHC class II.

Synonyms: activated CD8-positive, alpha-beta T lymphocyte, human, activated CD8-positive, alpha-beta T-cell, human, activated CD8-positive, alpha-beta T-lymphocyte, human, activated CD8+ T cell

Selected Context(s): Overall

Gene Significance Landscape

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Cell Significance Index (CSI) is uniquely calculated to reveal cell-specific gene markers. More info here

Significant Genes List

Genes with the highest and lowest Percentile Rank Scores (PRS) for activated CD8-positive, alpha-beta T cell, human within the selected context(s).

Gene ID: A unique numerical identifier for this specific gene.
Symbol: Shortened abbreviation or name that represents this gene.
Ensembl Gene ID: A unique identifier assigned by Ensembl for genomic data mapping.
CSI Score: A combined effect size and statistical significance measure for activated CD8-positive, alpha-beta T cell, human. Higher scores indicate a stronger, more significant difference in expression.
(Previously described as "Fold Change", but now represents Cliff's Delta × –log10(p).)

Gene ID: A unique numerical identifier for this specific gene.
Symbol: Shortened abbreviation or name that represents this gene.
Ensembl Gene ID: A unique identifier assigned by Ensembl for genomic data mapping.
CSI Score: A combined effect size and statistical significance measure for activated CD8-positive, alpha-beta T cell, human. Higher scores indicate a stronger, more significant difference in expression.
Average CSI: csi sum / gene count
Cell network configuration

This network visualizes key genes for activated CD8-positive, alpha-beta T cell, human. It primarily includes:
1. Top genes highly significant for this cell (Num. Top Cell Genes - based on the 'Min. CSI' setting).
2. Any additional specific 'Context Genes' you add below.
The final network is a combined view. Choose an Interaction Source (pathways or protein interactions) and optionally compare CSI scores with a Baseline Cell Type.

Maximum number of selected genes.
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Select a context for the target cell.
Target Cell for CSI:  activated CD8-positive, alpha-beta T cell, human (CL0001049)

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Nodes (Genes):
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Node size also reflects Target Cell CSI magnitude.
Node Color (Target Cell CSI in specific network):
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 High
 Medium
 Low
 Very Low
 N/A or Not Sig.
Edges (Interactions):
 STRING (Protein-Protein)
 ONTOLOGY (Shared Pathway)
 Colors vary by pathway category; default arrow applies.

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## Summary The [activated CD8-positive, alpha-beta T cell, human](/details-cell/CL0001049) is a cytotoxic lymphocyte characterized by a state of high metabolic activity and preparedness for effector function. Based on its gene significance profile, this cell type is defined by the highly specific expression of genes involved in energy production, protein synthesis, and immune modulation. The prominence of mitochondrial respiratory chain components like [COX1](/details-gene/4512) and [ATP6](/details-gene/4508), alongside genes controlling translation ([TPT1](/details-gene/7178)) and protein turnover ([UBC](/details-gene/7316)), suggests a cell that is metabolically primed to sustain the demanding processes of proliferation and cytotoxicity. A defining feature is the high expression of the non-classical MHC class I molecule [HLA E](/details-gene/3133), indicating a potential role in regulating the broader immune response through interactions with other lymphocytes. ## Key Characteristics and Function **Overall**, the gene expression landscape of the [activated CD8-positive, alpha-beta T cell, human](/details-cell/CL0001049) points to a cell in a state of heightened readiness, balancing robust biosynthetic capacity with regulatory control. The top markers can be grouped into several key functional clusters. * **High Metabolic and Biosynthetic Activity:** The cell's activated state is underpinned by a strong metabolic signature. The high specificity scores ([csi_z](/methods)) for multiple mitochondrial genes, including cytochrome c oxidase subunits ([COX1](/details-gene/4512), [COX2](/details-gene/4513)) and ATP synthase ([ATP6](/details-gene/4508)), are consistent with the immense energy requirement for effector functions. This is complemented by the prominent expression of genes essential for protein synthesis and turnover. These include translationally controlled tumor protein ([TPT1](/details-gene/7178)), ubiquitin genes ([UBC](/details-gene/7316), [UBB](/details-gene/7314)), and nucleophosmin ([NPM1](/details-gene/4869)), which is involved in ribosome biogenesis. This suggests a cell that is actively synthesizing proteins necessary for its cytotoxic role while also maintaining proteostasis. * **Transcriptional and Post-Transcriptional Regulation:** The cell's identity is further defined by transcription regulators. [BTG1](/details-gene/694), a known antiproliferative gene, is a top marker, suggesting the presence of intrinsic mechanisms to control clonal expansion following activation ([Link](https://doi.org/10.1002/j.1460-2075.1992.tb05213.x)). The presence of general transcription factor [BTF3](/details-gene/689) and multiple heterogeneous nuclear ribonucleoproteins like [HNRNPA2B1](/details-gene/3181) and [HNRNPDL](/details-gene/9987) highlights the active transcription and mRNA processing required to execute its effector program. * **Immune Modulation and Signaling:** A key characteristic is the high specific expression of [HLA E](/details-gene/3133). As a non-classical MHC class I molecule, [HLA E](/details-gene/3133) typically presents a restricted set of peptides and interacts with inhibitory receptors like CD94/NKG2A on NK cells and a subset of T cells. Its status as a top marker suggests that activated CD8+ T cells may actively participate in tempering the immune response, possibly to prevent excessive inflammation or autoimmunity ([Link](https://pubmed.ncbi.nlm.nih.gov/3131426/)). The strong signal for [CALM1](/details-gene/801) (calmodulin) underscores the central role of calcium signaling in maintaining the activated state. * **Cytoskeletal Dynamics:** Genes involved in cytoskeletal rearrangement, such as [CFL1](/details-gene/1072) (cofilin 1) and [MYL12A](/details-gene/10627) (myosin regulatory light chain), are also highly specific. This is consistent with the need for dynamic actin remodeling during T-cell migration, formation of the immunological synapse, and cell division. The profile of least significant markers helps to refine the cell's identity. The low specificity score for [TCF7](/details-gene/6932), a transcription factor critical for T-cell memory formation, may suggest this profile represents a state geared more towards immediate effector function rather than long-term memory commitment. Similarly, the low specificity of [KLRG1](/details-gene/10219), a marker of senescence, may indicate this activated state precedes terminal exhaustion. The negative significance of [RTN4](/details-gene/57142) (Nogo), a neurite outgrowth inhibitor, confirms its distinct lymphoid lineage and lack of neuronal function. ## Clinical Significance and Contextual Roles The gene signature of the [activated CD8-positive, alpha-beta T cell, human](/details-cell/CL0001049) provides insights into its potential roles in disease. The intense metabolic activity, highlighted by the prominence of mitochondrial genes, is a hallmark of effective anti-tumor and anti-viral responses. This metabolic state, however, can also be a point of vulnerability, as nutrient-poor tumor microenvironments can impair T-cell function. Therefore, genes like [COX1](/details-gene/4512) and [ATP6](/details-gene/4508) represent potential targets for immunometabolic therapies aimed at boosting T-cell persistence and efficacy. The high expression of [HLA E](/details-gene/3133) has significant clinical implications. In the context of cancer, tumor cells can upregulate [HLA E](/details-gene/3133) to engage inhibitory receptors on immune cells and evade destruction. The finding that activated CD8+ T cells themselves are a primary source of [HLA E](/details-gene/3133) suggests a complex regulatory network. This could represent a physiological brake on the immune response that might be exploited by pathogens or tumors. Furthermore, the expression of genes with dual roles in proliferation and regulation is noteworthy. [BTG1](/details-gene/694), an anti-proliferative factor whose locus is involved in chromosomal translocations in B-cell leukemia ([Link](https://doi.org/10.1002/j.1460-2075.1992.tb05213.x)), may serve as a critical checkpoint in activated T cells to prevent uncontrolled expansion. Its dysregulation could potentially contribute to T-cell lymphoproliferative disorders. The general ubiquity of many top markers, such as ubiquitin ([UBC](/details-gene/7316)) and ferritin ([FTL](/details-gene/2512)), underscores that T-cell activation co-opts fundamental cellular machinery to an exceptional degree, making these cells powerful but resource-intensive players in immunity. ## Potential Mechanisms and Research Directions 1. **Hypothesis:** The highly specific expression of the non-classical MHC molecule [HLA E](/details-gene/3133) by activated CD8+ T cells serves as a key feedback mechanism to regulate cytotoxic activity and prevent immunopathology. By presenting peptides and engaging inhibitory CD94/NKG2A receptors on adjacent NK cells and other T cells, these activated cells may actively limit the duration and intensity of the local immune response, thereby minimizing collateral damage to healthy tissue. * **Surprising Findings:** It is unexpected that [HLA E](/details-gene/3133), a molecule often associated with immune inhibition and NK cell regulation, emerges as a top specificity marker for *activated* cytotoxic T cells, rather than more canonical effector molecules like granzymes or perforin. * **Testable Questions:** Does the selective blockade of the [HLA E](/details-gene/3133):CD94/NKG2A interaction in a co-culture of activated CD8+ T cells and target cells lead to enhanced off-target cytotoxicity or prolonged effector activity compared to control conditions? 2. **Hypothesis:** The "activated" state of a [CD8-positive, alpha-beta T cell, human](/details-cell/CL0001049) is not a simple "on" switch but a tightly balanced condition of "controlled readiness." The co-dominant expression of genes driving high metabolic output (e.g., [COX1](/details-gene/4512), [ATP6](/details-gene/4508)) and protein synthesis ([TPT1](/details-gene/7178)) alongside potent anti-proliferative regulators (e.g., [BTG1](/details-gene/694)) suggests an intrinsic cellular program that primes the cell for rapid effector function while simultaneously imposing strict controls on cell cycle progression to ensure a measured and sustainable response. * **Surprising Findings:** The simultaneous high specificity of potent metabolic "accelerator" genes and cell cycle "brake" genes like [BTG1](/details-gene/694) is counterintuitive. It suggests the canonical view of activation as unchecked expansion may be an oversimplification, and that internal regulation is a defining, rather than a subsequent, feature of this state. * **Testable Questions:** In primary human CD8+ T cells, does CRISPR-mediated knockout of [BTG1](/details-gene/694) prior to activation result in a higher initial burst of proliferation followed by a more rapid decline in cell viability and function due to metabolic exhaustion or an inability to manage proteotoxic stress?