Mathew, Porunellor A.2019-08-222019-08-222001-11-012013-08-27https://hdl.handle.net/20.500.12503/29198Natural killer cells are a third population of lymphocytes, distinct from T and B cells. NK cells are non-MHC-restricted cytotoxic effector cells which are effective against intracellular pathogens, virally-infected cells and tumor cells. 2B4 is a natural killer cell receptor originally identified in the mouse as a surface molecule involved in non-MHC-restricted killing and enhancement of IFN-γ secretion. The human and rat homologues of 2B4 have recently been cloned in our laboratory. Interferon gamma (IFN-γ) is a cytokine with potent anti-viral and anti-proliferative effects. In addition, this cytokine acts as a global immune regulator by regulating gene expression and serving to attract other immune cells. In this work, we establish the function of human 2B4 in a NK cell line, YT. We have shown that human 2B4 activation induces cytolytic function and enhances IFN-γ release in YT cells. Additionally we show that 2B4’s regulation of IFN-γ occurs at the transcriptional level, both through mRNA stability and increased promoter activity. We also demonstrate that several regions in the IFN-γ promoter respond to 2B4 activation and IFN-γ both separately and together in the rejection of metastatictumor cells in C57B7/6 mice. Our results confirm that both 2B4 and IFN-γ are critical in the rejection of metastatic tumor cells. Through the use of activating monoclonal antibodies, our studies indicate that 2B4’s anti-tumor activity is through IFN-γ as well as through cytolytic function of NK cells.application/pdfenBiologyCell AnatomyCell and Developmental BiologyCell BiologyCellsCellular and Molecular PhysiologyGenetic PhenomenaGenetics and GenomicsImmunology and Infectious DiseaseLife SciencesMedical Cell BiologyMedical GeneticsMedical Molecular BiologyMedicine and Health SciencesMolecular BiologyOther Cell and Developmental BiologyNatural killer cellslymphocytesnon-MHC-restricted cytotoxic effector cellsIFN-y secretionhuman homologuesrat homologues2B4interferon gammacytokineanti-viralanti-proliferativemRNA stabilityanti-tumor activityDissertation