Tyrosine phosphorylation of the Fc gamma RIII(CD16): zeta complex in human natural killer cells. Induction by antibody-dependent cytotoxicity but not by natural killing.
NK cells are large granular lymphocytes capable of killing certain tumor cells and virally infected cells in a non-MHC-restricted manner. NK cells can also effect an antibody dependent cytotoxicity that is triggered by CD16, an FcR for IgG. In NK cells, CD16 is expressed in association with zeta, a signal transducing subunit of the TCR complex. Here we show that, just as T cell activation via the TCR complex results in tyrosine phosphorylation of zeta TCR, NK cell activation via CD16 results in tyrosine phosphorylation of zeta NK. Whereas antibody-dependent cytotoxicity also results in tyrosine phosphorylation of zeta, natural cytotoxicity does not. Our results indicate that zeta functions as a transducing element for antibody dependent, but not antibody independent killing by NK cells. Consequently, NK cells are likely to express at least two distinct receptor complexes capable of triggering cytolytic effector function.
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115.
E
E
Vivier
P
P
Morin
C
C
O'Brien
B
B
Druker
S F
SF
Schlossman
P
P
Anderson
D000920:Antibody-Dependent Cell Cytotoxicity; D015703:Antigens, CD / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000378:metabolism*; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins; D010766:Phosphorylation; D019000:Phosphotyrosine; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011961:Receptors, Fc / Q000378:metabolism*; D017452:Receptors, IgG; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D017452:Receptors, IgG; C054979:antigen T cell receptor, zeta chain; D019000:Phosphotyrosine; D014443:Tyrosine