FC-GAMMA RECEPTOR TYPE-III (CD16) IS INCLUDED IN THE ZETA-NK RECEPTOR COMPLEX EXPRESSED BY HUMAN NATURAL-KILLER-CELLS

We recently reported that CD3- natural killer (NK) cells express the ζ chain of the T-cell receptor complex (ζ NK) in association with higher molecular weight structures whose expression differs between individual NK cell clones. Because NK cell cytolytic activity is known to be triggered by perturbation of the type III Fc(γ) receptor (CD16), we sought to determine whether this activating molecule is included in the ζ NK molecular complex. Biochemical evidence for a physical association between CD16 and ζ NK was obtained by comparing immunoprecipitates formed using monoclonal antibodies reactive with each of these molecules by SDS/polyacrylamide gel electrophoresis, immunoblotting, and peptide mapping. In both clonal and polyclonal populations of CD3- NK cells, CD16 and ζ NK specifically associated with one another. Functional evidence for a specific association between CD16 and ζ NK in intact cells was obtained by demonstrating a coordinate down-modulation of both of these molecules induced by either phorbol 12-myristate 13-acetate or monoclonal antibodies reactive with CD16. Our results suggest that Fc(γ) receptor type III (CD16) is included in the ζ NK complex and that this complex is likely to play an important role in NK cell activation.