1. Wim Jennes, Sonja Verheyden, Julie W. Mertens, Makhtar Camara, Moussa Seydi, Tandakha N. Dieye, Souleymane Mboup, Christian Demanet, Luc Kestens Inhibitory KIR/HLA incompatibility between sexual partners confers protection against HIV-1 transmission Institute of Tropical Medicine Antwerp University Hospital Brussels Cheikh Anta Diop University of Dakar

2. Autoresponse: Natural killer cells kill founder HIV-1 infected CD4+ T-cells Alloresponse: Natural killer cells kill partner HIV-1 infected CD4+ T-cells How can NK cells protect against HIV-1 infection?

3. KIR/HLA typing in HIV-1 transmitting and non-transmitting married couples from Dakar, Senegal Autoresponse NK cell protection due to activating KIR and missing ligand combinations Alloresponse

4. KIR/HLA mismatched stem cell transplants cure leukemia Velardi et al, Curr Opin Immunol 2008; Moretta et al, Immunology Reviews 2008

5. KIR/HLA typing in HIV-1 transmitting and non-transmitting married couples from Dakar, Senegal Autoresponse NK cell protection due to activating KIR and missing ligand combinations NK cell protection due to missing self alloreactive KIR/HLA combinations Alloresponse

6. Summary and implications Summary o Lack of HIV-1 transmission in African couples is associated with - NK cell activating KIR/HLA genotypes in the recipient partner - KIR/HLA missing self combinations between partners o KIR/HLA missing self combinations correlate with alloreactive NK cell killing of HIV-1 patient-derived CD4+ T cells in vitro Implications o NK cells could be important in protection against HIV-1 infection and may be suitable targets for future preventive therapies o KIR/HLA mismatched stem cell transplants: revolution in leukemia Can KIR/HLA mismatches be exploited in HIV prevention and cure?