KLRC2 Antibody
Description
Definition and Biological Role
KLRC2 Antibody specifically binds to the NKG2C protein encoded by the KLRC2 gene, a type II transmembrane receptor expressed primarily on NK cells . NKG2C forms heterodimers with CD94 to recognize HLA-E molecules presenting pathogen-derived peptides, triggering cytotoxic responses against infected or malignant cells .
Key functional attributes:
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Immune activation: Binds HLA-E complexed with viral peptides (e.g., human cytomegalovirus) to activate NK cells
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Adaptive immunity: Drives clonal expansion of "memory-like" NK cells during chronic infections
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Therapeutic potential: Modulates tumor microenvironment in glioblastoma (GBM) by enhancing PD-1 inhibitor efficacy
Viral Infections
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CMV/HIV: Elevated NKG2C+ NK cells correlate with improved viral control . KLRC2 antibodies track NK cell memory formation in simian immunodeficiency virus (SIV) models .
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COVID-19: Low NKG2C+ NK cell counts predict CMV reactivation and mortality in severe cases .
Cancer Immunotherapy
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Glioblastoma: Tumor-expressed NKG2C enhances PD-1 inhibitor efficacy by recruiting cytotoxic lymphocytes .
Autoimmunity
Technical Considerations and Challenges
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Cross-reactivity: Traditional antibodies fail to distinguish NKG2C from NKG2A in non-human primates; RNA-based flow cytometry resolves this .
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Functional assays: Antibodies like FAB138F enable single-cell analysis of NKG2C/CD94 complexes in cytokine release assays .
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Storage: Most conjugates require -20°C storage with minimal freeze-thaw cycles .
Clinical Implications and Biomarker Potential
Future Directions
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Biomarker validation: Prospective trials needed to confirm NKG2C as a predictor for checkpoint inhibitor efficacy .
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Gene-edited therapies: CRISPR-modified NKG2C+ NK cells show promise in adoptive cancer immunotherapy .
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Multiplex panels: Combining KLRC2 antibodies with PD-1/PD-L1 markers could refine patient stratification .
Product Specs
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Target Background
KLRC2 encodes the NKG2C activating receptor, crucial for self-nonself discrimination within the immune system. In conjunction with KLRD1 on cytotoxic lymphocyte subsets, it recognizes non-classical major histocompatibility complex (MHC) class Ib HLA-E molecules loaded with signal sequence-derived peptides from non-classical MHC class Ib HLA-G molecules. This interaction plays a significant role in adaptive natural killer (NK) cell development and effector functions, and is implicated in maternal-fetal tolerance during pregnancy. NKG2C regulates the effector functions of terminally differentiated cytotoxic lymphocyte subsets, potentially contributing significantly to the adaptive NK cell response to viral infections. Upon binding to HLA-E-peptide complexes, intracellular signaling is initiated via the adaptor protein TYROBP/DAP12, leading to phosphorylation of proximal signaling molecules and subsequent cell activation.
KLRC2 Gene Function and Clinical Relevance: Selected Research Findings
- A 16kb deletion encompassing the NKG2C gene correlates with reduced carotid intimal media thickness and enhanced humoral and T-cell responses to cytomegalovirus (CMV) in renal transplant recipients. PMID: 28987961
- Studies have expanded the characterization of adaptive NK cell subsets differentiating in response to human CMV, indicating a relationship between their distribution and NKG2C copy number. PMID: 26994220
- A novel method allows the utilization of SNP array data from genome-wide association studies to investigate the frequency of KLRC2 deletion in various populations and its association with diverse diseases. PMID: 27312142
- Analysis of NK cell repertoires in 60 NKG2C(-/-) donors revealed a wide range of NK cell populations exhibiting characteristics of adaptive NK cells, including a terminally differentiated phenotype, functional reprogramming, and epigenetic remodeling of the interferon (IFN)-gamma promoter. PMID: 27117418
- HLA-E regulates NKG2C+ natural killer cell function through the presentation of a restricted peptide repertoire. PMID: 26382247
- Genetic polymorphism in KLRC2 is not associated with nasopharyngeal carcinoma in China. PMID: 25636564
- Evidence suggests the proinflammatory potential of NKG2C(bright) NK cells. PMID: 25667418
- Lack of NKG2C expression may be associated with altered control of human cytomegalovirus infection in childhood. PMID: 25150297
- No significant difference in the prevalence of NKG2C deletion was observed in a specific study. PMID: 24305414
- NKG2C receptor deletion and functional polymorphisms in its ligand HLA-E may contribute to psoriasis susceptibility. PMID: 24079744
- NKG2C(hi)CD57+ NK cells respond specifically to acute cytomegalovirus infection, not Epstein-Barr virus infection. PMID: 24740502
- NKG2C null genotype does not appear to be a risk factor for HPV-induced cervical lesions. PMID: 23911737
- NKG2C zygosity influences CD94/NKG2C receptor function and NK cell compartment redistribution in response to human cytomegalovirus. PMID: 24030638
- Co-expression of killer cell Ig-like receptor (KIR) and NKG2C on expanded NK cell subsets may indicate a functional role for KIR in cytomegalovirus infection. PMID: 23918974
- NKG2Chi CD57hi natural killer cells demonstrate high responsiveness to human cytomegalovirus-infected macrophages only in the presence of CMV-specific antibodies, but are less effective in natural cytotoxicity. PMID: 23637420
- Increased NKG2C expression in HIV patients suggests its importance in defense against HIV infection and progression. PMID: 22074011
- A significantly higher proportion of ex vivo peripheral blood CD4 T cells (but not CD8 T cells or NK cells) from multiple sclerosis patients express NKG2C, potentially contributing to tissue damage. PMID: 23396942
- HCMV-infected NKG2C(+/+) children exhibited higher absolute numbers of NKG2A(+) and total NK cells compared to NKG2C(+/-) individuals. PMID: 22965785
- NKG2C expression by Vdelta2+ T cells is lower in pregnant women. PMID: 19395088
- CD94/NKG2C may be involved in activating cytotoxic lymphocytes in patients with toxic epidermal necrolysis and Stevens-Johnson syndrome. PMID: 20132973
- NKG2C gene deletion is commonly observed in the general population. PMID: 12618865
- NKG2C is not essential for survival and reproduction and is not associated with rheumatic diseases. PMID: 14688071
- Strict gene regulatory mechanisms govern CD94 and NKG2 gene expression on CD4+ cells. PMID: 15550116
- CD94/NKG2C may represent an alternative T cell activation pathway capable of driving the expansion and effector functions of a cytotoxic T cell subset. PMID: 15940674
