Activation and selection of NK cells via recognition of an allogeneic, non-classical MHC class I molecule, RT1-E

Previous studies have established that NK cells express both inhibitory and activatory receptors. The inhibitory receptors have been shown to recogniz e major MHC class I molecules, but the physiological ligands for the activa tory receptors have been only partly characterized. In this study we invest igated whether NK cells could be activated by recognizing specific non-clas sical MHC class Ib molecules. NK cells from BN (RT1(n)) rats immunized in v ivo with MHC-incompatible WF (RT1(u)) cells displayed cytolytic activity sp ecific for product(s) of the MHC class Ib RT1-E-u/C-u region. These cells w ere shown to kill Rat2 fibroblast cells transfected with cDNA for RT1-E-u b ut neither untransfected Rat2 nor a transfectant with the class la allele, RT1-A(u). Cytolysis of Rat2-RT1-E-u was inhibited by the anti-RT1-E-u antib ody 70-3-C2. In addition, NK cells cytolytic against PVG (RT1(c)) targets, but not against WF (RT1(u)) or other allogeneic targets were activated afte r PVG immunization of BN rats. The generation of NK populations cytolytic f or target cells of the same haplotype as the immunizing cells, but not for third-party targets, strongly suggests the existence of a selective NK-medi ated response in vivo. We conclude that recognition of an allogeneic MHC cl ass Ib RT1-E molecule activates NK cells and the specific cytolytic respons e could be regarded as adaptive.