The HLA-DRA Knockout 769-P Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout population derived from the 769-P human clear cell renal cell carcinoma line. This product disrupts the HLA-DRA gene, which encodes the alpha chain of MHC class II HLA-DR, providing a loss-of-function model to dissect antigen presentation and immune recognition. The polyclonal cell pool maintains functional heterogeneity typical of CRISPR editing, offering a robust tool for reproducible functional assays without single-cell clonal selection.
The 769-P cell line is an epithelial model established from a primary clear cell renal cell carcinoma, a prevalent and aggressive kidney cancer subtype. It is widely used to investigate RCC biology, drug resistance, and tumor-microenvironment interactions, and features molecular hallmarks such as altered hypoxia signaling. This host background offers a clinically relevant platform to explore immune evasion mechanisms involving MHC class II.
HLA-DRA encodes the alpha subunit of the HLA-DR MHC class II heterodimer, which forms a peptide-presenting complex with HLA-DRB chains. Expression is regulated by the class II transactivator CIITA and the RFX complex (RFX5, RFXAP, RFXANK), and is induced by interferon gamma (IFNG). The assembled heterodimer associates with CD74 and, after endosomal editing by HLA-DM, presents antigens to CD4+ T cells. TCR engagement activates LCK and ZAP70 kinase cascades, propagating via LAT to drive T-cell activation and cytokine output such as IL-2 and IFNG. Cytokines including IL-4, IL-10, and TGF-??1 further modulate HLA-DR levels.
In the 769-P clear cell renal carcinoma line, CRISPR/Cas9-mediated disruption of HLA-DRA ablates surface HLA-DR expression, crippling antigen presentation to T helper cells. This recapitulates tumor-intrinsic MHC class II downregulation, a mechanism of immune evasion that limits CD4+ T-cell responses. Consequently, the model enables dissection of how RCC cells modulate adaptive immunity and permits testing of interventions designed to reinstate MHC class II-mediated anti-tumor activity.
Research applications include studying MHC class II antigen presentation in ccRCC, examining tumor-immune cell interactions via co-culture, and screening for compounds that alter HLA-DRA expression. Compatible assays include flow cytometry for surface protein analysis, western blotting, RT-qPCR, immunofluorescence, T-cell activation and cytokine ELISAs, and transcriptomic approaches such as RNA-seq. This polyclonal knockout system is suited for functional genomics and drug discovery efforts aimed at the MHC class II pathway in renal cancer. Additional technical information and ordering support are available from Ascent Research.
