Antibody Dependent Cell Mediated Cytotoxicity

Natural killer (NK) cells and other leukocytes bind to antibody-coated cells by Fc receptors and destroy these cells. This process is called antibody-dependent cellular cytotoxicity (ADCC) (Fig. 12-5). It was first described as a function of NK cells, which use their Fc receptor, FcyRIIIA, to bind to antibody-coated cells. FcyRIIIA (CD16) is a low-affinity receptor that binds clustered IgG molecules displayed on cell surfaces but does not bind circulating monomeric IgG. Therefore, ADCC occurs only when the target cell is coated with antibody molecules,

FIGURE 12-5 Antibody-dependent cell-mediated cytotoxicity. Antibodies of certain IgG subclasses bind to cells (e.g., infected cells), and the Fc regions of the bound antibodies are recognized by an Fcy receptor on NK cells. The NK cells are activated and kill the antibody-coated cells. Presumably, NK cells can lyse even class I MHC-expressing targets when these target cells are opsonized because the Fc receptor-mediated stimulation may overcome the inhibitory actions of class I MHC-recognizing NK cell inhibitory receptors (see Chapter 12).

Surface antigen

FcyRIII

Surface antigen

FcyRIII

Antibody-coated cell

NK cell

Antibody-coated cell

NK cell

Killing of antibody-coated cell and free IgG in plasma neither activates NK cells nor competes effectively with cell-bound IgG for binding to FcyRIII. Engagement of FcyRIII by antibody-coated target cells activates the NK cells to synthesize and secrete cytokines such as IFN-y as well as to discharge the contents of their granules, which mediate the killing functions of this cell type (see Chapter 4). ADCC can be readily demonstrated in vitro, but its role in host defense against microbes is not definitively established. It is likely an important mechanism for the elimination of cells that are coated by specific therapeutic monoclonal antibodies, such as B cells and B cell-derived tumor cells that are targeted by anti-CD20 antibody.

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