Early HIV-1 infection differentially alters responses of KIR-expressing Natural Killer cells in individuals carrying cognate HLA-C haplotypes (P6203)

Abstract

Abstract “NK cell licensing” describes the acquisition of functional competence of KIR-expressing NK cells in the presence of cognate HLA ligands. However, whether licensed NK cells contribute to the control of viral infections is not clear. Therefore, we investigated the response of KIR+ NK cells in association with cognate HLA-C haplotypes in HIV-1 infected individuals. 18 HLA-Bw4(-), KIR2DL1/2/3(+) patients with early HIV-1 infection have been enrolled. NK cell responses and KIR expression were measured by flow cytometry. NK cell responses were defined by levels of degranulation and cytokine production after co-incubation with 721.221 target cells. While the frequency of KIR2DL1+ NK cells was increased in the presence of the cognate C2C2 haplotype, the proportion of KIR2DL2/3+ NK cells was reduced as compared to individuals carrying the C1C1 or C1C2 haplotype (p<.05 for each). Of note, levels of degranulation and cytokine production of bulk NK cells did not differ among the three groups. However, within KIR2DL1+ NK cell subsets the C2C2 haplotype was associated with increased NK cell activity (p<.05), while the C1C1 haplotype had no effect on the respective KIR2DL2/3+ NK cell subset. Our results indicate a C2C2 haplotype-dependent expansion and increased responsiveness of KIR2DL1+ NK cells during early HIV-1 infection. A potentially more efficient licensing of KIR2DL1+ NK cells in C2C2 carriers might explain the observed increased responses in the setting of early HIV-1 infection.