The KLRB1 Knockout HAP1 Polyclonal Cells product consists of a CRISPR/Cas9-edited polyclonal knockout cell population targeting the KLRB1 gene in HAP1 cells. This model provides a genetically disrupted KLRB1 locus, enabling loss-of-function studies of the CD161 inhibitory receptor. The polyclonal format preserves cellular diversity while ensuring gene disruption across the population, suitable for functional genomics and signaling pathway analysis.
HAP1 is a human near-haploid cell line derived from chronic myeloid leukemia KBM-7 cells, exhibiting adherent fibroblast-like morphology and a near-haploid karyotype. Its haploid nature facilitates straightforward genetic manipulation and phenotyping, making it an ideal host for CRISPR-based knockout screens and targeted gene disruption studies. This cell line is widely employed in functional genomics, drug target discovery, and signal transduction research.
KLRB1 encodes CD161, an inhibitory C-type lectin-like receptor on NK cells and T cells. Ligand binding by LLT1 (CLEC2D) recruits SHP-1 phosphatase, which dephosphorylates ZAP70 and LAT, attenuating MAPK/ERK signaling and reducing cytotoxicity and cytokine production (IFN-??, TNF-??). Its regulation involves cytokines IL-12 and IL-15, and TCR engagement via CD3/CD28. The LLT1-KLRB1-SHP-1 axis constitutes an immune checkpoint modulating lymphocyte effector functions.
Disruption of KLRB1 in the HAP1 near-haploid background eliminates CD161 inhibitory signaling, enabling precise dissection of this checkpoint without diploid complexity. This model facilitates study of LLT1 interactions and phosphorylation events in the TCR/MAPK/ERK cascade.
Applications include functional genomics of immune checkpoints, NK and T cell exhaustion mechanisms, and drug target validation for cancer, autoimmunity, and inflammatory bowel disease. Assays such as flow cytometry for CD161, Western blot and co-IP for SHP-1 and phospho-proteins, RT-qPCR, cytotoxicity, cytokine multiplex, and reporter assays for NFAT/AP-1 are directly applicable. For technical inquiries, contact Ascent Research.
