The CD4 Knockout 769-P Polyclonal Cells are a CRISPR/Cas9-generated polyclonal knockout cell population derived from the 769-P human clear cell renal cell carcinoma line. This product features targeted disruption of the CD4 gene, encoding the T cell co-receptor and HIV receptor. The polyclonal nature yields a heterogeneous pool of cells with diverse loss-of-function mutations, permitting robust functional studies without clonal selection artifacts.
The 769-P cell line harbors a VHL tumor suppressor mutation and retains epithelial morphology typical of clear cell renal carcinoma. It is widely employed in kidney cancer and hypoxia research. Introduction of CD4 knockout into this tumorigenic background enables investigation of non?canonical CD4 functions in epithelial tumor biology, including potential contributions to immune evasion and cell signaling.
CD4 functions as a co-receptor for MHC class II, amplifying T cell receptor (TCR) signaling upon antigen recognition. Its cytoplasmic tail associates with the tyrosine kinase Lck, which phosphorylates the CD3 complex and ZAP70, initiating a signaling cascade that involves LAT, PLC??1, and PKC??. This leads to activation of transcription factors NFAT, NF-??B, and AP-1, which orchestrate immune responses. HIV gp120 utilizes CD4 as the primary entry receptor, while IL?16 also binds CD4, highlighting its role in cell communication. The pathway is further regulated by TCR stimulation, MHC class II engagement, and coreceptor availability.
In the 769-P renal carcinoma context, CD4 ablation provides a unique tool to examine tumor?intrinsic roles of CD4. Ectopic CD4 expression has been documented in certain carcinomas, and this knockout facilitates dissection of CD4?dependent signaling independent of lymphoid cells. The polyclonal design supports bulk analyses of CD4?mediated effects on tumor cell behavior, HIV susceptibility, and interactions with immune cells.
Typical applications include HIV pseudovirus infection assays to verify loss of viral entry, co?culture systems with T lymphocytes to study tumor?immune crosstalk, and cytokine profiling to assess immune modulatory capacity. Molecular validation uses Western blotting, flow cytometry, and RT?qPCR. This polyclonal knockout population is suited for drug response studies, signaling pathway analyses, and interrogation of CD4 in antigen presentation. For further inquiries, contact Ascent Research.
