PREFERENTIAL INVOLVEMENT OF G(O) AND G(Z) PROTEINS IN MEDIATING RAT NATURAL-KILLER-CELL LYSIS OF ALLOGENEIC AND TUMOR TARGET-CELLS

IL-2-activated NK cells from PVG rats potently lyse target cells expre ssing allo-MHC class I determinants, Here, we investigated the role th at G proteins play in mediating this activity, Pretreatment of NK cell s with pertussis toxin (PT) or cholera toxin (CT) inhibited NK cell ki lling of tumor (YAC-1 or P815), and allogeneic target cells, ADP ribos ylation assay revealed that PT ADP ribosylates a 39-kDa G protein, whe reas CT ADP ribosylates a 45 to 47-kDa G protein in PVG NK cell membra nes, Membranes prepared from intoxicated NK cells with either PT or CT lost their ability to incorporate [P-32]NAD, These membranes possess G(i), G(o), G(s), and G(z) as demonstrated by immunoblot analysis, How ever, G(q) was not clearly detected by this method, IL-2-activated NK cells were permeabilized with streptolysin O. Permeabilized cells inco rporated Abs to G(i), G(o), G(z), G(s), and G(q) as determined by flow cytometric analysis, When Abs to G(o) or G(z), but not to G(i), G(s), or G(q), were incorporated inside permeabilized NK cells, a significa nt reduction in the lysis of tumor or allo-MHC target cells was observ ed, suggesting that G(o) and G(z) play important roles in transducing the signals necessary to lyse target cells, Our results show for the f irst time a role for G proteins in mediating NK cell killing of allo-M HC-encoded target cells, and provide evidence for G(z) protein involve ment in NK cell recognition of target cells. The effect of G(z) is nov el and has not been previously described in any other system or cell t ype.