Grant: Doctoral Research Award - PA: Biomedical/Clinical HIV/AIDS Research

HIV infection causes AIDS and is one of the top 3 global infectious disease killers. Some people remain uninfected despite multiple exposures to the virus. Of those who become infected, about 5% progress slowly without treatment. Epidemiological studies implicate Natural Killer (NK) cells in HIV resistance and slow time to AIDS in those infected. These protective outcomes are associated with expressing certain NK cell surface receptors called KIRs and their ligands, HLA molecules. KIR and HLA interact with each other to determine how active an NK cell will be when it recognizes virus infected cells. Previous work from Dr. Bernard's group has demonstrated that NK cells from individuals with protective KIR/HLA genotypes had larger numbers of NK cells with stronger and multiple anti-viral functions. My Ph.D. research will extend this work by identifying which NK cell subset/s respond to HIV infected cells and confer protective outcomes in the context of HIV. I will develop and optimize tools to detect NK cell subsets based on patterns of KIR expression and assess the function of these subsets. I will have access to cells from subjects who are HIV uninfected and HIV positive typical and slow progressors typed for KIR and HLA variants. I will determine which NK cells subsets are activated by HIV infected cells versus by cell stimuli that activate NK cells more broadly (as well as controls). The effect of HIV infection status, KIR/HLA genotype and stimulus on NK function will be measured and compared in terms of frequency of the activated subset/s, intensity of function and number of functions among NK subsets. Results from this project should deepen our understanding of how NK cells respond to HIV infected cells and how this differs according to KIR/HLA genotypes that are or are not protective. A better understanding of how NK cells function to prevent infection may aid in developing strategies that harness NK cells to prevent HIV infection.