Molecular Characterization of NKp44 Ligand on Astrocytes

Abstract AIDS is a major health problem in the world with more than 36 million people living with HIV infection. HIV can invade the central nervous system (CNS) infecting resident macrophages, microglial cells, and astrocytes leading to neurologic complications. Although the use of highly active antiretroviral therapy (HAART) has led to a strong reduction of HAD incidence, the prevalence of minor HAD AND HAND still remains a common problem in AIDS patients. Natural Killer (NK) cells play a critical role in immune responses to CNS injury. NK cell activity controls CNS autoimmunity and inflammation by their ability to kill proinflammatory microglia. NK cells may also impact CNS physiology by secreting IFN-­?. Astrocytes are intimately involved in immunological and inflammatory events occurring in the CNS. The impact of NK-­astrocyte interactions in regulation of immune response in the brain is poorly understood. Our preliminary data showed that Natural Cytotoxicity Receptor (NCR) NKp44 interacts with a novel ligand expressed on astrocytes. There is a critical need to understand the functional significance of NK cells in the CNS during HIV infection and their interactions with astrocytes. Characterization of this novel ligand for NKp44 could lead to new insight into NK cell mediated immune response against HIV infection in the CNS. In this study, using mammalian expression cloning we will clone this ligand using NKp44-­Fc fusion protein. We will also investigate the functional outcome of NKp44 ligand expressed on astrocytes interaction with NKp44 in regulating immune response mediated by NK cells. Here, we will determine the effect of NKp44 receptor/ligand interaction on NK cell cytolytic function and IFN-­? production. Characterization of this novel ligand could lead to new insight into NK cell mediated immune response against HIV infection in the CNS.