Natural Killer Cell Responses to HIV-1 Peptides are Associated With More Activating KIR Genes and HLA-C Genes of the C1 Allotype

作者：Tiemessen Caroline T^*; Paximadis Maria; Minevich Gregory; Winchester Robert; Shalekoff Sharon; Gray Glenda E; Sherman Gayle G; Coovadia Ashraf H; Kuhn Louise

来源：JAIDS: Journal of Acquired Immune Deficiency Syndromes , 2011, 57(3): 181-189.

DOI：10.1097/QAI.0b013e3182174a76

• HIV-specific NK cell responses
• KIR
• HLA-B
• HLA-C

Background: What characterizes individuals whose natural killer (NK) cells are able to respond to HIV-1 peptides is not known.
Methods: The association between NK cell responses and KIR gene profiles and HLA-B and HLA-C alleles was investigated among 76 HIV-1-infected women in South Africa previously categorized as responders (n = 39) or nonresponders (n = 37) to HIV-1 peptide pools in a whole blood intracellular cytokine assay. Viral load was significantly lower and CD4 T-cell counts higher among responders compared with nonresponders (P = 0.023 and P = 0.030, respectively).
Results: Possession of one HLA-C1 allele associated with increased magnitude of NK cell responses to Env (P = 0.031) and significantly decreased viral load (P = 0.027) compared with its absence. There was a trend to increased possession of KIR2DL3+HLA-C1 in responders (71.8% vs 51.4%, P = 0.098) and decreased possession of KIR2DL3/2DL3+C2C2 (2.6% vs 16.2%, P = 0.053). A total of 64.1% of responders versus 32.4% of nonresponders had 13 or more KIR genes (P = 0.0067). Notably, the 13-KIR gene containing the Bx21 genotype (has eight inhibitory and three activating genes KIR2DS2, 2DS4, 2DS5) showed substantially higher representation among the responders (28.2% vs 2.6%, P = 0.001). A significantly higher proportion of responders had both KIR2DS2 and KIR2DS5 compared with either gene alone (72.4% vs 37%; P = 0.015). At least one HLA-C1 allele together with 13 or more KIR genes was associated with NK cell responsiveness (48.7% vs 13.5%; P = 0.001).
Conclusion: NK cell responses to HIV-1 peptides are more likely to occur among individuals with a genotype supporting a more activating NK cell phenotype and who possess at least one HLA-C1 allele.

• 出版日期2011-7-1