Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2007 Jun;39(6):733-40.
doi: 10.1038/ng2035. Epub 2007 May 13.

Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1

Maureen P Martin  1 , Ying Qi, Xiaojiang Gao, Eriko Yamada, Jeffrey N Martin, Florencia Pereyra, Sara Colombo, Elizabeth E Brown, W Lesley Shupert, John Phair, James J Goedert, Susan Buchbinder, Gregory D Kirk, Amalio Telenti, Mark Connors, Stephen J O'Brien, Bruce D Walker, Peter Parham, Steven G Deeks, Daniel W McVicar, Mary Carrington
Affiliations
Multicenter Study

Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1

Maureen P Martin et al. Nat Genet. 2007 Jun.

Abstract

Allotypes of the natural killer (NK) cell receptor KIR3DL1 vary in both NK cell expression patterns and inhibitory capacity upon binding to their ligands, HLA-B Bw4 molecules, present on target cells. Using a sample size of over 1,500 human immunodeficiency virus (HIV)+ individuals, we show that various distinct allelic combinations of the KIR3DL1 and HLA-B loci significantly and strongly influence both AIDS progression and plasma HIV RNA abundance in a consistent manner. These genetic data correlate very well with previously defined functional differences that distinguish KIR3DL1 allotypes. The various epistatic effects observed here for common, distinct KIR3DL1 and HLA-B Bw4 combinations are unprecedented with regard to any pair of genetic loci in human disease, and indicate that NK cells may have a critical role in the natural history of HIV infection.

PubMed Disclaimer

Conflict of interest statement

COMPETING INTERESTS STATEMENT

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
Allele frequency of KIR3DL1 alleles and HLA-B Bw4 subtypes. The frequency of each variable is shown for African Americans and European Americans.
Figure 2
Figure 2
Effect of KIR3DL1*004 + HLA-B Bw4 on AIDS progression. Individuals with KIR3DL1*004 and Bw4 and those lacking this compound genotype were compared with individuals homozygous for HLA-Bw6 for two AIDS outcomes. The subjects were seroconverters of all racial groups in combined cohorts. Relative hazard (RH) and significance (P) are given for Cox proportional model analyses.
Figure 3
Figure 3
Effect of KIR3DL1 + HLA-B Bw4 genotypes on progression to CD4+ T-cell count < 200 cells/mm3. (a) KIR3DL1 genotypes with Bw4-80I. (b) KIR3DL1 genotypes with Bw4-80T. Relative hazard (RH) and P values are based on comparisons between the specific genetic variables listed and Bw6/Bw6. The KIR3DL1*h/*y group includes KIR3DL1*h/*h and KIR3DL1*h/*004 individuals, and the KIR3DL1*l/*x group includes KIR3DL1*l/*l, KIR3DL1*l/*h and KIR3DL1*l/*004 individuals.
Figure 4
Figure 4
Synergistic influence of specific HLA-B allotypes with KIR3DL1*h and KIR3DL1*l genotypes on progression to two AIDS outcomes. (a) HLA-B*57; (b)HLA-B*27. Bw6/Bw6 individuals were used as the control group in each analysis. The number of individuals in each category is shown below the bars. The KIR3DL1*h/*y group includes KIR3DL1*h/*h and KIR3DL1*h/*004 individuals, and the KIR3DL1*l/*x group includes KIR3DL1*l/*l, KIR3DL1*l/*h and KIR3DL1*l/*004 individuals.
Figure 5
Figure 5
KIR3DL1 + Bw4 continuum of protection. Genotypes are ordered by degree of protection in terms of (a) disease progression and (b) control of viral load. The most protective genotypes are shown on the right of the vertical scale and the alternative (less protective) genotypes are shown on the left. (a) Relative hazard ranges for the two AIDS outcomes (CD4+ T-cell count < 200 cells/mm3 and AIDS1987) relative to the Bw6/Bw6 control group. (b) Odds ratios (dots) of protective genotypes relative to the Bw6/Bw6 control group in terms of their distributions in the < 2,000 versus the > 10,000 MVL groupings. Purple bars and dots, B*57 with KIR3DL1 genotypes; green bars and dots, B*27 with KIR3DL1 genotypes; light blue bars and dots, Bw4-80I with KIR3DL1 genotypes; dark blue bar, Bw4-80I+KIR3DS1; yellow bars, Bw4 with or without KIR3DL1*004.
See this image and copyright information in PMC

Comment in

References

    1. Biron CA, Nguyen KB, Pien GC, Cousens LP, Salazar-Mather TP. Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol. 1999;17:189–220. - PubMed
    1. Lanier LL. NK cell recognition. Annu Rev Immunol. 2005;23:225–274. - PubMed
    1. Colucci F, Di Santo JP, Leibson PJ. Natural killer cell activation in mice and men: different triggers for similar weapons? Nat Immunol. 2002;3:807–813. - PubMed
    1. Vilches C, Parham P. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol. 2002;20:217–251. - PubMed
    1. Gumperz JE, et al. Conserved and variable residues within the Bw4 motif of HLA-B make separable contributions to recognition by the NKB1 killer cell-inhibitory receptor. J Immunol. 1997;158:5237–5241. - PubMed

Publication types

MeSH terms