Immunregulation

The research group ‘Immunoregulation’ aims to understand the regulation of NK cells on a molecular level. NK cells have two main effector functions – cellular cytotoxicity and the production of cytokines. While cytokine production can be induced in NK cells upon exposure to pro-inflammatory cytokines, direct contact to other cells is the main stimulus for the induction of cellular cytotoxicity. Signals emanating from cell surface receptors are essential for the regulation of both processes. We therefore apply modern analytical methods to study human NK cells and how the activity of these cells is regulated through signals by different cell surface receptors.

How are NK cells activated?

The activation of NK cells can be triggered by a multitude of different receptors such as NKp46, NKp44, NKp30, NKp80, NKp65, 2B4, CS1/CRACC, NTB-A, DNAM-1 and NKG2D (see figure 1). NKG2D, NKp46, NKp44, and NKp30 associate with ITAM-containing polypeptides such as DAP12 or the CD3zeta chain and NKG2D also associates with the signaling partner DAP10. In contrast, 2B4 contains 4 so called ITSM motifs (Immunoreceptor Tyrosine-based Switch Motif) in its cytoplasmic tail. ITSM motifs can also be found in CS1/CRACC and NTB-A. We are studying the signal transduction of these different NK cell receptors to determine how they contribute to NK cell activity. Furthermore we are investigating how the signals from activating and inhibitory receptors are integrated on a molecular level inside NK cells. Our ultimate goal is to understand the regulation of these important immune cells and to find ways to manipulate NK cell activity.

Signal transduction of the SLAM-related receptors (SRR) 2B4, CRACC and NTB-A

How do members of the SLAM-related receptor (SRR) family activate NK cells and also other immune cells? Our goal is to study the ligand interaction and signal transduction of these receptors in different immune cells and to determine the functional impact of SRR on NK and T cells.

How are positive and negative signals integrated?

In this project we study the early signal transduction of activating and inhibitory receptors in a combination of experimental approaches and mathematical modeling.

What is the role of membrane microdomains (lipid rafts) in NK cells?

We are interested in the functional role of membrane microdomains (lipid rafts) during the regulation of NK cell activity. For this we are utilizing different modern techniques to isolate these domains, to study their lipid and protein composition and to investigate the recruitment of activating receptors in these domains. For more information see also:

How do the different activating ligands contribute to NK cell activity?

In this project we study the impact of different activating and inhibitory ligands on target cells on NK cell activity. By comparing the quantitative impact of these different stimuli we aim to better predict NK cell reactivity against tumors.