Index: Karolinska Institutet: KI South: Department of Medicine, Huddinge
Activating KIR receptors in antiviral defense
Natural killer (NK) cells represent the largest proportion of innate effector Lymphocytes and account for 10-15% of total peripheral lymphocytes. In contrast to T and B cells, NK cells do not require pre-activation but can instantly kill virally infected & transformed cells, by detecting molecular sings of cellular stress and the absence of HLA expression in the cell surface. This unique capability of an immediate and efficient response towards tumor and virally infected cells initiated many anti-tumor therapies, which work as a proof of principle. Of crucial importance for the functional regulation of human NK cells are Killer cell immunoglobulin like receptors (KIR). These receptors can be either activating or inhibitory in nature. While the function and the ligands to the inhibitory KIR receptors are well studied, activating KIRs are poorly understood. Previous findings suggest a protective role of activating KIRs from viral infections. In parallel a protection from different malignancies has been suggested. Work of our and other groups suggest that activating KIRs are especially involved in the recognition of human herpes viruses. Using reporter cell lines, we will investigate the presence of ligands to activating KIR receptors in virally infected target cells. After confirmation of the presence of aKIR ligands in virally infected cells, we aim to investigate if the ligand is presented in an HLA dependent or independent manner. Subsequent goals are the identification of a ligand and/or assessing the role of activating KIRs in triggering an immune response e.g. by regulating formation of the immunological synapse in NK cells. Chance to learn/get insight in the following techniques - Flow cytometry including phosphoflow - Functional and killing assays with NK cells - Cell culture - Western blot - Confocal microscopy |