A7 - HCV infection: Mechanisms of NK-cell-mediated control

A7_April 2014

Principal investigator:
Prof. Dr. med. Marcus Altfeld
Head, Research Unit Viral Immunology
Heinrich Pette Institute (HPI)
Leibniz Institute for Experimental Virology
Martinistraße 52
20251 Hamburg
Tel.: +49-40-48051-221
E mail: marcus.altfeld@hpi.uni-hamburg.de

Participating staff:

Dr. rer. nat. Sebastian Lunemann – PostDoc
Urte Matschl – Techical Assistant
Arne Düsedau – Technical Assistant
Leonhard Hess- M.D. Student
Pia Fittje – Ph.D. Student

Project description

Natural Killer (NK) cells are a central component of the early immune responses against viruses and malignancies, and highly enriched in the liver. However, the contribution of NK cells to liver inflammation, and their role in liver disease pathogenesis and viral hepatitis are still unclear. The hypothesis underlying the project is that NK cell diversity can determine the clinical course of HCV infection.

We plan to characterize NK cell diversity by multiparameter flow cytometry in peripheral blood and liver of HCV-infected individuals with different disease outcomes. We will translate these findings in collaborative studies within CRC 841 to assess the interactions between NK cell diversity and liver inflammation and to determine the receptor/ligand interactions involved.

A7 in 60 SecondsVideoarchiv

online seit 23.02.2014

Previous studies have demonstrated that specific genotypes of NK cell receptors (Killer cell-Immunoglobulin-like receptors, or KIRs) in conjunction with their HLA class I ligands are associated with a better outcome of HCV infection. We furthermore showed that NK cells expressing these KIRs are preferentially expanded in individuals with cleared HCV infection.
We now plan to determine how these KIR+ NK cells recognize HCV-infected cells, and how HCV can evade this NK cell-mediated immune selection pressure.

Related news:

Martrus G, Kautz T, Lunemann S, Richert L, Glau L, Salzberger W, Goebels H, Langeneckert A, Hess L, Poch T, Schramm C, Oldhafer KJ, Koch M, Tolosa E, Nashan B, Altfeld M.

Proliferative capacity exhibited by human liver-resident CD49a+CD25+ NK cells
PLoS One. 2017 Aug 9;12(8):e0182532. doi:10.1371/journal.pone.0182532. eCollection 2017

Lunemann S, Martrus G, Goebels H, Kautz T, Langeneckert A, Salzberger W, Koch M, J Bunders M, Nashan B, van Gisbergen KPJM, Altfeld M

Hobit expression by a subset of human liver-resident CD56 Natural Killer cells
Sci Rep. 2017 Jul 27;7(1):6676. doi: 10.1038/s41598-017-06011 7.

Lunemann S, Martrus G, Hölzemer A, Chapel A, Ziegler M, Körner C, Beltran WG, Carrington M, Wedemeyer H, Altfeld M

Sequence variations in HCV core-derived epitopes alter binding of KIR2DL3 to HLA-C(∗)03:04 and modulate NK cell function
J Hepatol. 2016 Apr 4. pii: S0168-8278(16)30097-6. doi:10.1016/j.jhep.2016.03.016. [Epub ahead of print]

Video abstract english "Sequence variations in HCV core-derived epitopes...Videoarchiv

online seit 07.06.2016

Jost S, Altfeld M

Control of human viral infections by natural killer cells
Annu Rev Immunol. 2013;31:163-94. doi: 10.1146/annurev-immunol-032712-100001. Epub 2013 Jan 3.