Natural killer (NK) cell receptor-HLA ligand genotype combinations associated with protection from HIV infection: investigation of how protective genotypes influence anti HIV NK cell functions.

The anti-HIV activity of natural killer (NK) cells could be induced fast enough to potentially prevent the establishment of HIV infection. Epidemiological studies identified two genotypes encoding NK receptors that contribute to NK cell function, that were more frequent in people who remained uninfected despite multiple HIV exposures than in HIV-susceptible subjects. NK cells from carriers of the *h/*y+B*57 genotype have higher NK cell functional potential and inhibit HIV replication in autologous HIV-infected CD4+ T cells (iCD4) more potently than those from carriers of non-protective genotypes. HIV suppression depends on the secretion of CC-chemokines that block HIV entry into CD4+ cells. NK cell education and the effect of HIV infection on iCD4 cell surface expression of MHC-I antigens both influenced NK cell responses to autologous iCD4. The second KIR3DS1 homozygous protective genotype encodes an activating receptor that upon interacting with its HLA-F ligand on iCD4 induces anti-viral activity.