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CUTTING EDGE |
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* Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium;
HLA Laboratory, Academisch Ziekenhuis-Vrije Universiteit Brussel, Brussels, Belgium;
Projet RETRO-CI, Abidjan, Côte d’Ivoire;
Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA.
NK cells are regulated in part by killer Ig-like receptors (KIR) that interact with HLA molecules on potential target cells. KIR and HLA loci are highly polymorphic and certain KIR/HLA combinations were found to protect against HIV disease progression. We show in this study that KIR/HLA interactions also influence resistance to HIV transmission. HIV-exposed but seronegative female sex workers in Abidjan, Côte d’Ivoire, frequently possessed inhibitory KIR genes in the absence of their cognate HLA genes: KIR2DL2/KIR2DL3 heterozygosity in the absence of HLA-C1 and KIR3DL1 homozygosity in the absence of HLA-Bw4. HIV-seropositive female sex workers were characterized by corresponding inhibitory KIR/HLA pairings: KIR2DL3 homozygosity together with HLA-C1 and a trend toward KIR3DL1/HLA-Bw4 homozygosity. Absence of ligands for inhibitory KIR could lower the threshold for NK cell activation. In addition, exposed seronegatives more frequently possessed AB KIR genotypes, which contain more activating KIR. The data support an important role for NK cells and KIR/HLA interactions in antiviral immunity.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Belgian Fund for Scientific Research (FWO-Vlaanderen), Grant G.0660.06, and the Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, Atlanta, GA. S.V. was supported by a grant from the Scientific Fund W. Gepts AZ-VUB.
2 W.J. and S.V. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Wim Jennes, Department of Microbiology, Laboratory of Immunology, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerpen, Belgium. E-mail address: wjennes{at}itg.be
4 Abbreviations used in this paper: KIR, killer Ig-like receptor; ESN, HIV-exposed seronegative; FBD, female blood donor; FSW, female sex worker; SP, HIV-1-seropositivep; CI, confidence interval.
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