The KLRB1 Knockout NCI-H1703 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which the gene encoding the inhibitory NK cell receptor NKG2A (KLRB1) has been disrupted. This product provides a heterogeneous pool of NCI-H1703 cells carrying diverse loss-of-function mutations at the target locus, generated without single-cell cloning, enabling the study of NKG2A deficiency in a physiologically relevant cancer model. The polyclonal format captures the complexity of genetic perturbation across the population, making it suitable for functional genomics screens, immune checkpoint investigations, and tumor?Cimmune cell interaction analyses.
NCI-H1703 is a human lung squamous cell carcinoma line derived from a 54-year-old male, serving as a well-characterized non-small cell lung cancer (NSCLC) model. This adherent epithelial line retains key features of squamous cell lung cancer and is widely employed in preclinical oncology research. The use of NCI-H1703 as the host background for KLRB1 disruption provides a clinically relevant cellular context for interrogating the role of NKG2A in tumor biology, particularly in the setting of immune evasion mechanisms exploited by lung carcinomas.
KLRB1 encodes NKG2A, a C-type lectin-like receptor that forms a disulfide-linked heterodimer with CD94. The CD94/NKG2A complex functions as an inhibitory receptor by specifically recognizing the non-classical MHC class I molecule HLA-E. Upon ligand engagement, NKG2A recruits the tyrosine phosphatases SHP-1 and SHP-2 via immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytoplasmic tail. These phosphatases dephosphorylate key signaling intermediates, including Vav-1, thereby counteracting activation signals downstream of Syk and ZAP70. This inhibitory cascade suppresses natural killer (NK) cell and CD8+ T-cell cytotoxicity, promoting immune tolerance. KLRB1 expression is regulated by cytokines such as TGF-beta, IL-12, and IL-15, and by the transcription factors T-bet and Eomes, which act upstream to modulate NKG2A levels during immune cell development and response.
In the context of NCI-H1703 lung squamous carcinoma cells, KLRB1 knockout eliminates NKG2A-mediated inhibitory tone, creating a genetic background in which the receptor’s contribution to tumor-immune crosstalk can be dissected. This model is particularly relevant for studying how tumor cells upregulate HLA-E to engage NKG2A on infiltrating lymphocytes and dampen anti-tumor immunity. By disrupting the receptor directly in the tumor line, researchers can assess cell-autonomous effects and, when combined with co-culture experiments, explore how the absence of NKG2A alters immune cell recognition and killing.
This knockout cell product is ideally suited for cancer immunotherapy research, NK cell functional analysis, and immune checkpoint target validation. Typical applications include NK cell cytotoxicity assays, antibody-dependent cellular cytotoxicity (ADCC) reporter assays, flow cytometry for NKG2A expression, co-culture tumor cell killing assays, and western blotting for SHP-1/SHP-2 phosphorylation. The polyclonal knockout population enables robust assessment of the KLRB1 axis in NCI-H1703 cells, supporting tumor microenvironment studies and the dissection of inhibitory receptor signaling pathways. For detailed product specifications and ordering information, please contact Ascent Research.
