Since the introduction of Antiretroviral Therapy (ART), life expectancy in HIV-1 infected people drastically improved, as morbidity and mortality decreased. However, the virus persists in viral reservoirs due to several evasion mechanisms of the virus, such as HLA downregulation by Nef and Vpu and the impairment of T cell function. HIV-1 latency leads to a chronic state of immune activation and inflammation, affecting the quality of immune responses to HIV-1 and other pathogens. Because the downregulation by Nef is incomplete and its effect on CTL epitope presentation varies between the different CTL epitopes, some HIV peptides are still presented despite the downregulation of HLA and can therefore still induce an immune response. Several HIV-1 peptides referred to as ´Nef-resistant´ have been identified by project B3. Complementary work in AG Nganou has demonstrated that targeting inflammatory or T cell exhaustion pathways can improve recall responses to prior antigens. In this project, we aim to study and counteract the effect of inflammation and immune activation on T cell responses to both HIV (e.g. Nef-resistant CTL epitopes) and de novo antigens. Findings of these projects may help identify biomarkers predicting responses HIV-1 and new antigens.
