The KLRB1 Knockout A2780 Polyclonal Cells are a pool of A2780 human ovarian carcinoma cells subjected to CRISPR/Cas9-mediated disruption of the KLRB1 gene, which encodes the inhibitory immune receptor CD161. This polyclonal knockout population comprises a heterogeneous mixture of cells carrying diverse indels at the target locus, providing a robust loss-of-function model without clonal selection. The product is designed for researchers investigating the role of CD161 in ovarian cancer biology and tumor-immune interactions, enabling potent and sustained gene silencing across a representative cell population.
The parental A2780 cell line is a well-characterized model of human ovarian endometrioid adenocarcinoma, originally established from an untreated patient. It harbors wild-type p53 and retains epithelial morphology and key signaling pathways relevant to ovarian malignancy. The A2780 line is widely used for studying ovarian cancer pathogenesis, drug response, and immune evasion mechanisms, making it an ideal host for engineering knockout models to explore tumor-intrinsic immune modulators.
KLRB1 encodes CD161, a C-type lectin-like inhibitory receptor expressed on natural killer cells and subsets of T cells. Upon engagement of its ligand CLEC2D (LLT1), CD161 transmits inhibitory signals through its cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM). This recruits the tyrosine phosphatases PTPN6 (SHP-1) and PTPN11 (SHP-2), which dephosphorylate proximal kinases including LCK and ZAP70, thereby attenuating early TCR signaling and downstream effectors such as VAV1 and PLCG1. CD161 expression is regulated by cytokines like IL-2 and IL-15 and by transcription factors T-bet (TBX21) and Eomesodermin (EOMES), linking its function to immune cell activation and effector programs. Disruption of KLRB1 abrogates this inhibitory circuit, leading to relief of negative regulation on key signaling nodes.
In the A2780 ovarian carcinoma background, KLRB1 knockout permits direct investigation of tumor cell-intrinsic CD161 functions that may extend beyond its canonical roles in immune cells. Ovarian tumors can exploit CD161-LLT1 interactions to dampen anti-tumor immunity, and A2780 cells may express both CD161 and its ligand, creating autocrine or paracrine signaling circuits. Ablation of KLRB1 eliminates CD161-mediated inhibitory signaling, potentially altering phospho-signaling networks and sensitizing tumor cells to immune effector mechanisms. This model thus provides a valuable platform to dissect how tumor-expressed CD161 influences immune evasion, cytokine production, and response to immunotherapies.
Typical applications include functional genomics studies using co-culture assays with NK cells or T lymphocytes to assess altered cytotoxicity, phospho-signaling analysis to map pathways downstream of CD161, and RNA-seq to profile global transcriptional changes. The cells are also suited for drug target validation and screening of therapeutic agents aimed at disrupting CD161-mediated immune checkpoints. Standard characterization assays such as Western blotting, RT-qPCR, and flow cytometry confirm knockout efficiency at the protein and transcript levels. For inquiries regarding lot-specific performance and technical guidance, please contact Ascent Research.
