Grant: Operating Grant

Some people remain HIV uninfected despite multiple exposures to this virus. The term HIV exposed seronegative (HESN) has been used to describe such individuals. By comparing HESN to HIV susceptible subjects we previously identified two genotypes coding for variants of Natural Killer (NK) cell receptors (NKR) and their ligands (the molecules recognized by NKR) that were associated with protection from HIV infection. NK cells are part of the innate arm of the immune system, which means that they are primed and ready to kill HIV infected cells, and secrete factors with anti-HIV activity. As such they have the kind of functional profile needed to act early to prevent the establishment of HIV infection. In this project we will continue our examination of how NK cells and autologous HIV infected cells (i.e. cells from the same person) interact to stimulate NK cells for anti-HIV activity. We will investigate the NKR profile of the NK cell subsets activated by autologous HIV infected cells, what ligands for NKR are induced by HIV infection and what stage of the HIV life cycle NK cell inhibit. We will also explore the potential and limitations of an NK cell function that links the innate and adaptive arms of the immune response. This function, if better understood, may be exploited to trigger protective immunity in a vaccine setting.