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

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?

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

KIR/HLA mismatched stem cell transplants cure leukemia

Velardi et al, Curr Opin Immunol 2008; Moretta et al, Immunology Reviews 2008

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

Summary and implications

Summaryo 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

Implicationso 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 leukemiaCan KIR/HLA mismatches be exploited in HIV prevention and cure?