Grant: Fellowship - PA: Biomedical / Clinical HIV/AIDS Research

Natural killer (NK) cells are a key player in innate immunity. There is evidence they play a role in host defenses to viruses such as HIV. NK cells have surface receptors called KIR that recognize HIV infected cells through binding some cell surface molecules on infected cells. These molecules, called HLA, are present on the surface of most cells in the body, including those that HIV targets in an infected person. NK cells can control infection by killing the HIV-infected cells and inhibiting HIV replication when the number of HLA molecules that KIR receptors recognize is downregulated by HIV in infected cells. The KIR receptors and HLA molecules have many variants that differ from one person to another and influence the functions of NK cells when they meet a target cell infected with HIV. There are KIR/HLA variants that are seen more frequently in people who remain uninfected despite exposure to HIV (exposed uninfected or EU subjects) than in HIV susceptible individuals. I hypothesize that the mechanism underlying why cetain KIR/HLA variants are associated with protection from infection is that NK cells from people expressing protective KIR/HLA variants are more readily activated to kill cells infected with HIV or prevent HIV from replicating and spreading. In this project I will study the anti-viral functions of NK cells from both individuals carrying certain KIR/HLA combinations associated with protection from HIV infection and individuals not carrying these combinations. This project will contribute to understanding the mechanism of protection from HIV infection in EUs and may provide clues on how to prepare HIV vaccines to reduce the risk of HIV infection.