THE ROLE OF CALNEXIN IN NK-TARGET CELL-INTERACTION

In this study, a relationship between target cell sensitivity to natur al killing and target cell expression of the molecular chaperon calnex in was assessed. The NK-resistant cell line NKR was originally derived from the NK-sensitive, human T-cell line CEM and does not synthesize calnexin protein or mRNA. The cell lines CEM, NKR and 1B9 (NKR transfe cted with a calnexin cDNA) were compared in a number of assays. All th e lines but CEM were resistant to NK in conventional 4 h cytotoxicity assay, but were highly sensitive to IL-2 activated NK. Incubation of N K cells with CEM but not with the other two lines led to increased exp ression of the NK cell activation marker CD69. Treatment of effector c ells with PGE(2) and TGF-beta resulted in an inhibition of NK activity and CD69 expression. The calnexin transfected clone 1B9 clone had int ermediate ability to block cytotoxicity in cold target inhibition assa y compared to CEM and NKR. Expression of the adhesion molecules CD44 a nd LFA-1 alpha was significantly higher on both calnexin positive cell lines compared to NKR. These data suggest that calnexin controls the expression of some, but not all, target structures that are necessary for binding and activation of NK cells. Published by Elsevier Science B.V. All rights reserved.