26 July 2016 - PRESS RELEASE
How killer cells identify HIV-1 infected cells
A team of researchers from the Heinrich Pette Institute and the USA have succeeded in identifying a protein called HLA-F which functions as the ligand of an activating natural killer cell receptor. This functional interaction could explain why the cell receptor is associated with a range of human disease outcomes, including those of HIV infection. The results are now published in Nature Immunology.
Virus-infected cells have to express infection markers on their cell surfaces so that they can be identified by cells of the immune system. "KIR3DS1" is an activating receptor found on the plasma membrane of natural killer cells. In HIV infections, this receptor is associated with a delayed progression of disease. The corresponding ligand on the infected cells has remained unknown up to now. The researchers have now screened one hundred different HLA-1 proteins and were able to identify HLA-F as the ligand of the receptor.
Biochemical and functional investigations have shown that contact between the KIR3DS1 receptor and the HLA-F ligand increases antiviral cytokine production in natural killer cells and inhibits the in vitro replication of HIV-1. HIV infection further increases HLA-F transcription but simultaneously decreases binding of the KIR3DS1 receptor to HIV infected cells. The scientists suspect this to be a viral mechanism for evading the immune system.
“Our investigations have shown that HLA-F is a high-affinity ligand of the cell receptor KIR3DS1," explains DZIF scientist Prof Marcus Altfeld, Head of the Research Unit "Virus Immunology" at the HPI.
Garcia-Beltran WF; Hölzemer A; Martus 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: Open confomers of HLA-F are high-affinity ligands of the activating natural killer-cell receptor KIR3DS1. Nature Immunology 2016; 25. Juli 2016. doi:10.1038/ni.3513
Prof Marcus Altfeld
Heinrich Pette Institute