Epidemiological studies showed that combinations of alleles encoding Natural Killer (NK) cell receptors and their ligands influence time to AIDS in HIV infected individuals. Since NK cells, as part of the innate immune system, are primed to rapidly respond to activating signals there was a rationale for the possibility that NK cells also play a role in preventing HIV infection. My seminar will describe the findings generated by multiple trainees over several years. This body of work provided support for the hypothesis that certain NK receptor-ligand combinations are associated with a reduced likelihood of HIV infection despite high levels of exposure to this virus. The research program explored how the genetics of NK cell receptor-ligand combinations translates into the potency of anti-HIV NK cell function.