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Previously unknown interaction suggests role of HLA class II molecules as regulators of innate immune responses
Hamburg. A scientific team from the Research Department of Virus Immunology at the Heinrich Pette Institute, Leibniz Institute for Experimental Virology (HPI) has investigated the binding of NK cell receptors to HLA class II molecules. The results have now been published in the renowned journal "Nature Immunology".
Natural killer cells (NK cells) can recognize virus-infected and stressed cells with the help of activating and inhibitory receptors. Many of these receptors interact with human leukocyte antigen (HLA) class I molecules on the cell surface. Although early studies have also suggested a functional influence of HLA class II molecules on NK cell activity, no NK cell receptor has yet been identified that specifically recognizes HLA class II molecules.
Researchers from the HPI Research Department of Virus Immunology under the leadership of Prof. Marcus Altfeld have now investigated whether two large families of NK cell receptors (killer cell immunoglobulin-like receptors and natural cytotoxicity receptors) contain receptors that can bind to HLA class II molecules.
The results, now published in the renowned journal "Nature Immunology", show a direct interaction between the activating NK cell receptor NKp44 and a subset of HLA class II molecules, including the HLA molecule HLA-DP401, one of the most abundant HLA-DP molecules in Caucasians.
"Our results show a previously unknown interaction between a number of HLA-DP molecules and the NK cell receptor NKp44. This interaction suggests an influence of HLA class II molecules on the regulation of innate immune cells", explains Annika Niehrs, first author of the publication and PhD student at the HPI.
"This newly identified interaction now enables the functional assessment of the consequences of these interactions for disease outcomes associated with HLA-DP genotypes. These include, for example, infections with the hepatitis B virus and inflammatory intestinal diseases", adds Prof. Marcus Altfeld, Head of the HPI Research Department “Virus Immunology” and Coordinator of the HIV Research Area at the German Center for Infection Research (DZIF).
This study, led by the Heinrich Pette Institute, was conducted as part of a DZIF project (TTU 04.810) and supported by the Federal Funds of the Frederick National Laboratory for Cancer Research.
The results were published in the journal „Nature Immunology“:
Annika Niehrs, Wilfredo F. Garcia-Beltran, Paul J. Norman, Gabrielle M. Watson, Angelique Hölzemer, Anais Chapel, Laura Richert, Andreas Pommerening-Röser, Christian Körner, Mikki Ozawa, Gloria Martus, Jamie Rossjohn, Jar-How Lee, Richard Berry, Mary Carrington, Marcus Altfeld (2019). A subset of HLA-DP molecules serve as ligands for the natural cytotoxicity receptor NKp44. Nature Immunology, 2019 July. DOI: 10.1038/s41590-019-0448-4
Annika Niehrs:
annika.niehrs@leibniz-hpi.de
Heinrich Pette Institute, Leibniz Institute for Experimental Virology,
Hamburg
Prof. Marcus Altfeld:
marcus.altfeld@leibniz-hpi.de
Heinrich Pette Institute, Leibniz Institute for Experimental Virology,
Hamburg
https://doi.org/10.1038/s41590-019-0448-4
https://www.hpi-hamburg.de HPI-Webseite
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