KLRB1 Human

What is the expression pattern of KLRB1 across normal human tissues?

KLRB1 shows variable expression across human tissues, with highest expression in immune tissues. According to the Genotypic Tissue Expression (GTEx) database analysis, KLRB1 is predominantly expressed in cells of the immune system, particularly natural killer (NK) cells and subsets of T cells . The protein expression pattern can be visualized through immunohistochemistry using resources like The Human Protein Atlas (THPA), which confirms its predominant expression in immune cells with specific subcellular localization patterns .

Methodologically, researchers should consider:

• Using RNA sequencing data from repositories like GTEx for tissue-level expression analysis

• Employing immunohistochemistry for cellular and subcellular localization studies

• Complementing with flow cytometry to quantify expression on specific immune cell populations

How is KLRB1 expression regulated in immune cells?

KLRB1 expression is dynamically regulated during immune cell differentiation. Research indicates that KLRB1 is one of the first markers acquired during CD4+ memory T cell differentiation . The regulation involves complex transcriptional networks associated with T cell maturation and activation states.

For studying KLRB1 regulation, researchers should:

• Apply single-cell RNA sequencing to track expression changes during differentiation

• Use chromatin immunoprecipitation (ChIP) to identify transcriptional regulators

• Employ reporter assays to validate specific regulatory elements controlling KLRB1 expression

What are the primary biological functions of KLRB1 in the human immune system?

KLRB1 plays crucial roles in immune response regulation. Gene Ontology (GO) and KEGG pathway analyses reveal that KLRB1 is significantly associated with:

• Immune response pathways, including adaptive and innate immune responses

• Lymphocyte-mediated immunity

• T cell receptor complex function

• Cytokine-cytokine receptor interaction

Functionally, KLRB1 expression correlates with immune checkpoint markers including CD40, CTLA4, CD44, and CD28, suggesting its involvement in immune regulation circuits . It also correlates with metagenomic clusters associated with hematopoietic cell kinase, lymphocyte-specific kinase (LCK), major histocompatibility complex, and STAT1/2 signaling .

How does KLRB1 expression differ across cancer types and what are the implications?

KLRB1 expression shows distinct patterns across cancer types, with significant clinical implications:

• In testicular germ cell tumors (TGCT), KLRB1 is upregulated compared to normal tissues, with higher expression in seminoma compared to other subtypes

• Lung adenocarcinoma (LUAD) shows reduced KLRB1 expression compared to normal lung tissue

• Endometrial cancer (EC) demonstrates lower KLRB1 mRNA expression than control tissues

• In hepatocellular carcinoma (HCC), KLRB1 expression on peripheral blood NK and T cells is down-regulated

Researchers investigating cancer-specific KLRB1 patterns should:

• Perform comparative analysis across multiple cancer databases (TCGA, GTEx)

• Stratify expression by cancer subtypes and stages

• Correlate expression with clinical parameters for prognostic assessment

What is the diagnostic and prognostic value of KLRB1 in cancer research?

KLRB1 shows considerable diagnostic and prognostic potential across several cancers:

• In TGCT, KLRB1 enrichment in seminoma yields an area under the ROC curve of 85.1%, making it a potential seminoma biomarker

• For LUAD, reduced KLRB1 expression positively correlates with tumor size, distant metastasis, pathological stage, and poorer survival outcomes

• In EC, high KLRB1 expression associates with better prognosis and correlates with cancer stage, ethnicity, weight, and histological subtypes

• For HCC, KLRB1 expression on NK and CD8+ T cells shows prognostic significance when evaluated using ROC analysis

Methodological approach for evaluating KLRB1 as a biomarker:

• Perform ROC analysis to determine sensitivity and specificity

• Conduct multivariate survival analysis to assess independent prognostic value

• Validate findings across independent cohorts using similar methodologies

How does KLRB1 interact with the tumor immune microenvironment?

KLRB1 demonstrates significant associations with tumor immune microenvironment components:

• KLRB1 expression negatively correlates with tumor purity and positively correlates with immune infiltration by B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells

• Changes in KLRB1 copy number significantly affect immune infiltration levels in cancer tissues

• KLRB1 expression associates with stromal, immune, and estimate scores in cancer analysis

• KLRB1 positively correlates with immune checkpoint markers, suggesting involvement in immune regulation networks

For analyzing KLRB1 in the tumor microenvironment, researchers should:

• Use tools like TIMER (Tumor Immune Estimation Resource) for immune infiltration analysis

• Conduct multiplex immunofluorescence to visualize spatial relationships between KLRB1+ cells and other immune populations

• Employ single-cell technologies to characterize KLRB1+ cells within the tumor microenvironment

How does KLRB1 expression change during T cell differentiation pathways?

KLRB1 shows a specific pattern during T cell differentiation:

• It is one of the first markers acquired during CD4+ memory T cell differentiation

• Its expression, in combination with other markers like KLRG1, GPR56, and KLRF1, allows classification of memory T cells into functional states: "low," "medium," "high," or "exhausted" cytokine producers

• The KLRB1+KLRG1+GPR56+KLRF1- T cell subset demonstrates the highest cytokine production potential, particularly for TNF-α/IFN-γ co-producing cells

Experimental approach for studying KLRB1 in T cell differentiation:

• Use flow cytometry with co-staining for KLRB1, KLRG1, GPR56, and KLRF1

• Apply single-cell gene expression profiling to identify transition states

• Perform functional assays to measure cytokine production in different KLRB1+ subpopulations

What methodologies are most effective for functional analysis of KLRB1+ T cells?

For comprehensive functional analysis of KLRB1+ T cells, researchers should consider:

• Isolation techniques:

  • Fluorescence-activated cell sorting (FACS) based on KLRB1 expression

  • Magnetic separation using anti-KLRB1 antibodies

• Functional assays:

  • Cytokine production analysis by intracellular staining or ELISA

  • Proliferation assays using CFSE dilution

  • Cytotoxicity assays against relevant target cells

• Molecular analysis:

  • Transcriptomic profiling of sorted KLRB1+ populations

  • Epigenetic analysis to identify regulatory regions

  • Proteomic analysis of signaling pathways

How do various combinations of KLRB1 with other markers define functional T cell subsets?

Research demonstrates that KLRB1 expression, when analyzed in combination with other markers, defines functionally distinct T cell populations:

This refined classification allows more precise identification of functionally relevant T cell subsets than traditional memory T cell categorization .

What signaling pathways are associated with KLRB1 function in immune cells?

KLRB1 associates with several key signaling pathways in immune cells:

• Gene Ontology (GO) analysis reveals association with:

  • Immune response pathways

  • Adaptive and innate immune responses

  • Plasma membrane signaling components

• KEGG pathway analysis shows enrichment in:

  • Tuberculosis pathway

  • Leishmaniasis pathway

  • Inflammatory bowel disease pathway

  • NF-κB signaling

  • PD-L1/PD-1 checkpoint pathways

• Correlation with metagenomic clusters related to:

  • Hematopoietic cell kinase

  • Lymphocyte-specific kinase (LCK)

  • STAT1/2 signaling

  • Interferon signaling

For investigating KLRB1 signaling, researchers should:

• Use phospho-flow cytometry to detect pathway activation

• Apply chemical inhibitors to block specific pathways

• Employ CRISPR-Cas9 to knock out pathway components

How does KLRB1 expression impact cellular proliferation and apoptosis in cancer models?

Research indicates that KLRB1 influences cancer cell biology in several ways:

• Overexpression of KLRB1 inhibits proliferation, migration, and invasion of lung adenocarcinoma cells

• KLRB1 overexpression promotes apoptosis in cancer cell models

• The mechanistic effects appear to involve immune-related pathways and potentially direct effects on cell cycle progression

Experimental approach for studying KLRB1's effects on cancer cells:

• Generate stable KLRB1 overexpression and knockdown cell lines

• Perform proliferation assays (MTT, BrdU incorporation)

• Analyze cell cycle distribution by flow cytometry

• Conduct apoptosis assays (Annexin V/PI staining)

• Use migration and invasion assays (transwell, wound healing)

What are the critical knowledge gaps in understanding KLRB1's role in human diseases?

Despite significant advances, several knowledge gaps remain in KLRB1 research:

• Mechanistic understanding:

  • Precise molecular mechanisms by which KLRB1 regulates immune cell function

  • Ligand-receptor interactions in different tissue contexts

  • Signaling pathways downstream of KLRB1 activation

• Clinical applications:

  • Standardization of KLRB1 assessment methodologies for clinical use

  • Validation of KLRB1 as a biomarker across diverse patient populations

  • Development of therapeutic approaches targeting KLRB1

• Disease contexts:

  • Role of KLRB1 in autoimmune diseases

  • Function in non-cancer pathologies

  • Tissue-specific roles beyond immune cells

What emerging technologies are advancing KLRB1 research?

Recent technological advances are accelerating KLRB1 research:

• Single-cell technologies:

  • Single-cell RNA sequencing for high-resolution expression profiling

  • Mass cytometry (CyTOF) for deep phenotyping of KLRB1+ cells

  • Spatial transcriptomics to understand KLRB1+ cells in tissue context

• Functional genomics:

  • CRISPR-Cas9 screening to identify regulators of KLRB1 expression

  • CRISPR activation/inhibition to modulate KLRB1 levels

  • Epigenetic profiling to understand regulatory mechanisms

• Computational approaches:

  • Machine learning for biomarker development

  • Network analysis to identify KLRB1-associated pathways

  • Multi-omics integration for comprehensive understanding

How might KLRB1 be targeted therapeutically in cancer and immune disorders?

Potential therapeutic approaches targeting KLRB1 include:

• Direct targeting:

  • Monoclonal antibodies modulating KLRB1 function

  • Small molecule inhibitors of KLRB1 signaling

  • Gene therapy approaches to regulate KLRB1 expression

• Combination strategies:

  • Combining KLRB1-targeted therapies with checkpoint inhibitors

  • Using KLRB1 expression as a biomarker for patient stratification

  • Manipulating KLRB1+ cells for adoptive cell therapy

• Research needs:

  • Development of specific KLRB1 agonists/antagonists

  • In vivo models to test therapeutic efficacy

  • Clinical trials to validate KLRB1-targeted approaches