The HPS3 Knockout Jurkat Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population designed to disrupt the HPS3 gene. This loss-of-function model provides a powerful tool for investigating HPS3-dependent processes in a human T-lymphoblast background. The Jurkat host line is well-suited for immunological studies, and the polyclonal format ensures a robust, heterogeneous population for bulk assays. This product enables dissection of lysosome-related organelle biogenesis and T-cell cytotoxicity without clonal selection.
Jurkat cells, derived from an acute T-cell leukemia patient, are immortalized human T lymphocytes widely used in immunology research. These cells respond to T-cell receptor activation, phorbol esters (PMA), and ionomycin, facilitating studies on signal transduction and effector functions. Their genetic tractability and reproducible growth make them ideal recipients for CRISPR-mediated gene disruption, allowing researchers to interrogate pathways involved in T-cell activation, cytokine production, and cytotoxic granule release.
HPS3 is a subunit of the BLOC-2 complex, which orchestrates cargo trafficking to lysosome-related organelles. It interacts with HPS5, HPS6, Rab32, Rab38, AP-3, BLOC-1, and clathrin to regulate endosomal sorting and lytic granule maturation. In T cells, TCR signaling or PMA/ionomycin stimulation triggers BLOC-2-dependent CD107a surface exposure and secretion of perforin and granzyme B. HPS3 disruption impairs BLOC-2 function, blocking lytic granule biogenesis and cytotoxic capacity. This knockout model reflects the molecular defects underlying Hermansky-Pudlak syndrome type 3.
In Jurkat cells, HPS3 loss directly compromises T-cell cytotoxicity, recapitulating the immunodeficiency seen in HPS3 patients. This model enables investigation of lysosomal trafficking defects and their impact on secretory granule formation. The polyclonal population avoids clonal artifacts, making it suitable for pharmacological studies targeting lysosomal pathways. By linking BLOC-2 dysfunction to immune cell activity, it provides a platform for exploring disease mechanisms and potential therapeutic interventions.
Applications include flow cytometry for CD107a degranulation, western blotting for HPS3, perforin/granzyme B secretion assays, electron microscopy of lytic granules, and cell-killing assays. Further studies may employ immunofluorescence for organelle markers, lysosomal pH measurement, or drug screening. This knockout cell population is suitable for research on Hermansky-Pudlak syndrome, T-cell cytotoxicity, and platelet dense granule biogenesis. For further information, please contact Ascent Research.
