Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1.

Journal Article (Journal Article)

The activating natural killer (NK)-cell receptor KIR3DS1 has been linked to the outcome of various human diseases, including delayed progression of disease caused by human immunodeficiency virus type 1 (HIV-1), yet a ligand that would account for its biological effects has remained unknown. We screened 100 HLA class I proteins and found that KIR3DS1 bound to HLA-F, a result we confirmed biochemically and functionally. Primary human KIR3DS1(+) NK cells degranulated and produced antiviral cytokines after encountering HLA-F and inhibited HIV-1 replication in vitro. Activation of CD4(+) T cells triggered the transcription and surface expression of HLA-F mRNA and HLA-F protein, respectively, and induced binding of KIR3DS1. HIV-1 infection further increased the transcription of HLA-F mRNA but decreased the binding of KIR3DS1, indicative of a mechanism for evading recognition by KIR3DS1(+) NK cells. Thus, we have established HLA-F as a ligand of KIR3DS1 and have demonstrated cell-context-dependent expression of HLA-F that might explain the widespread influence of KIR3DS1 in human disease.

Full Text

Duke Authors

Cited Authors

  • Garcia-Beltran, WF; Hölzemer, A; Martrus, G; Chung, AW; Pacheco, Y; Simoneau, CR; Rucevic, M; Lamothe-Molina, PA; Pertel, T; Kim, T-E; Dugan, H; Alter, G; Dechanet-Merville, J; Jost, S; Carrington, M; Altfeld, M

Published Date

  • September 2016

Published In

Volume / Issue

  • 17 / 9

Start / End Page

  • 1067 - 1074

PubMed ID

  • 27455421

Pubmed Central ID

  • PMC4992421

Electronic International Standard Serial Number (EISSN)

  • 1529-2916

Digital Object Identifier (DOI)

  • 10.1038/ni.3513


  • eng

Conference Location

  • United States