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Differential natural killer cell–mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes

2007/11/19 by Galit Alter, Maureen P. Martin, Nickolas Teigen +11 · 1 citation
Immunology and Microbiology · #Immune Cell Function and Interaction #HIV Research and Treatment #Reproductive System and Pregnancy

paper · pdf · doi:10.1084/jem.20070695

openalex publication_date 2007/11/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

Decline of peak viremia during acute HIV-1 infection occurs before the development of vigorous adaptive immunity, and the level of decline correlates inversely with the rate of AIDS progression, implicating a potential role for the innate immune response in determining disease outcome. The combined expression of an activating natural killer (NK) cell receptor, the killer immunoglobulin-like receptor (KIR) 3DS1, and its presumed ligand, human leukocyte antigen (HLA)-B Bw4-80I, has been associated in epidemiological studies with a slow progression to AIDS. We examined the functional ability of NK cells to differentially control HIV-1 replication in vitro based on their KIR and HLA types. NK cells expressing KIR3DS1 showed strong, significant dose- and cell contact-dependent inhibition of HIV-1 replication in target cells expressing HLA-B Bw4-80I compared with NK cells that did not express KIR3DS1. Furthermore, KIR3DS1+ NK cells and NKLs were preferentially activated, and lysed HIV-1 infected target cells in an HLA-B Bw4-80I-dependent manner. These data provide the first functional evidence that variation at the KIR locus influences the effectiveness of NK cell activity in the containment of viral replication.

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