title: Natural killer cell responses to HIV-1 peptides are associated with more activating KIR genes and HLA-C genes of the C1 allotype.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Institute for Communicable Diseases, Johannesburg, South Africa. carolinet@nicd.ac.za
authors.forename: Caroline T
authors.initials: CT
authors.lastname: Tiemessen
authors.forename: Maria
authors.initials: M
authors.lastname: Paximadis
authors.forename: Gregory
authors.initials: G
authors.lastname: Minevich
authors.forename: Robert
authors.initials: R
authors.lastname: Winchester
authors.forename: Sharon
authors.initials: S
authors.lastname: Shalekoff
authors.forename: Glenda E
authors.initials: GE
authors.lastname: Gray
authors.forename: Gayle G
authors.initials: GG
authors.lastname: Sherman
authors.forename: Ashraf H
authors.initials: AH
authors.lastname: Coovadia
authors.forename: Louise
authors.initials: L
authors.lastname: Kuhn
mesh_terms: D004279:DNA, Viral / Q000097:blood / Q000302:isolation & purification; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000276:immunology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015235:HLA-B Antigens / Q000235:genetics / Q000378:metabolism; D015236:HLA-C Antigens / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology*; D054340:Receptors, KIR / Q000235:genetics* / Q000378:metabolism; D054342:Receptors, KIR2DL1 / Q000502:physiology; D013019:South Africa / Q000453:epidemiology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D004279:DNA, Viral; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D054340:Receptors, KIR; D054342:Receptors, KIR2DL1; D054299:env Gene Products, Human Immunodeficiency Virus