[Frontiers in Bioscience 17, 1418-1432, January 1, 2012]

Molecular mechanisms of natural killer cell regulation

Carsten Watzll, 2, Doris Urlaubl

lInstitute for Immunology, University Heidelberg, INF 305, 69120 Heidelberg, Germany, 2Leibniz Research Center for Working Environment and Human Factors-IfADo, Ardeystrasse 67, 44139 Dortmund, Germany

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. NK cell activation
3.1. ITAM-based receptors
3.2. NKG2D
3.3. SLAM-family receptors
3.4. Complexity and robustness of NK cell activation
3.5. Common signaling pathways in NK cell activation
4. NK cell inhibition
4.1. Inhibitory receptors
4.2. ITIM signaling
4.3. NK cell education
5. Signal integration in NK cells
5.1. What do inhibitory receptors inhibit?
5.2. Integration of activating and inhibitory signals: The Vav1 Hypothesis
6. Mathematical approaches to NK cell regulation
7. Future challenges
8. Acknowledgements
9. References

1. ABSTRACT

Natural Killer (NK) cells are important for early immune reactions against viral infections and cancer. They are regulated by a highly redundant system of different activating and inhibitory receptors. Here we summarize our current understanding about the regulation of these cells and describe how mathematical modeling and systems biology approaches can help to shed some light on the complex regulatory network that governs NK cell reactivity.