J.T. Vaage

The NKRG research group focuses on the biology and recognition mechanisms of Natural Killer (NK) cells, which constitute an important part of our innate immune defence against neoplastic and virally infected cells, and normal allogeneic cells. Both the group leader and a senior scientist in the group have clinical functions in the Section of Transplantation Immunology, and NKRG is synergistically embedded in an environment of clinical and experimental immunology and histocompatibility testing. The research is performed in close collaboration with Prof. Bent Rolstad at the Department of Anatomy. The two laboratories are located within walking distance within the Gaustad campus and function as a combined group with regular joint meetings and sharing of resources.

One focus has been on the characterization of two families of lectin-like receptors on NK cells. The NKR-P1 family were among the first NK receptors to be identified, but were for long elusive. We have characterized their ligand-binding properties in rats and mice and have demonstrated phylogenetic and functional conservation in the two species (Kveberg, Eur.J.Immunol, 2009  and Immunogenetics 2011 ). The aim of future studies is to obtain a better understanding of their roles in NK cell biology and in immune responses against diseased cells, e.g. in a model of chronic inflammation (eosinophilic gastroenteritis).

A parallell goal is to characterize the repertoire of  activating Ly49 receptors for MHC class I ligands, which induce dramatic NK cell expansions upon repeated allostimulation in vivo (Dai, manuscript in preparation). The Ly49 receptors are functional homologues of the KIR receptors in primates. The rat model provided the first functional evidence that NK cells express activating receptors for polymorphic MHC class I molecules, mediating rejection of leukocyte allografts (Vaage, J.Exp.Med. 1994). These receptors were later shown to be Ly49 molecules (Naper, J.Immunol. 2002,2005), that in recent studies have been shown to recognize cells infected with the intracellular bacterium Listeria monocytogenes (Shegarfi, Eur.J.Immunol. 2010, J. Leuk. Biol. 2011, Naper. J. Innate Immun. 2011 [review]).

In a related line of experiments, we are focussing on the differential expression of Ly49 and NKR-P1 receptors by different subsets of NK cells and with unique functional characteristics (Kveberg, J.Immunol. 2006 ,  J. Leuk. Biol. 2010 ). We have recently identified a novel NK subset with an activated phenotype that is specifically enriched in gut-associated lymphoid organs (PP and mesenteric lymph nodes), liver and peripheral blood  (Inngjerdingen, Tissue Antigens 2011 [review] and submitted). Other projects include receptor-mediated signalling, effects of allogeneic stem cell transplantation on NK cell education and tolerance (Naper, International Immunology, 2010), and cellular therapy of experimental Acute Myelogenous Leukemia (BNML) and Graft-versus-Host (GvH) disease (Nestvold, Transplantation 2008, Zinöcker, PLoS ONE, 2011).