The role of Natural Killer cells in defense against pathogens.

Natural Killer (NK) cells represent an efficient first line defense mechanism against infected cells and certain cancer cells. For this purpose each NK cell is equipped with an array of activating and inhibitory receptors recognizing MHC class I and other molecules on their target cells. Although some of these receptors have now been molecularly characterized, we still have an incomplete picture of the repertoire of NK cell receptors and their ligands on target cells. Also there is a gap in our understand ing of how these different receptors collaborate to identify diseased cells. The main scope of this application is to gain more insight into these mechanisms by 1) identifying novel NK receptors and ligands, and 2) studying how these NK receptors recogniz e changes in ligand expression on diseased cells. The introduction of expression-based methods has enabled us to rapidly proceed from NK receptor and ligand characterization at the molecular level to studies of receptor function in vitro and in vivo. Here , we focus our studies on the role of NK receptors in resistance against intracellular pathogens Listeria Monocytogenes and Cytomegalovirus (CMV). The early defense against these microbes is dependent on NK cells, but the mechanisms of recognition of infe cted cells are not fully understood. The rat experimental model offers a unique system to test the role of these receptors in defense against this bacterium, as preliminary data show that some of the activating NK receptors may recognize MHC-modifications on infected cells. Hopefully, further exploration of this system will enable us to gain a better understanding of the role of NK cells in defense against infected cells in general.