antibody-dependent cellular cytotoxicity
Meaning of antibody-dependent cellular cytotoxicity: The immune system's way of using antibodies as handles, letting killer cells grip a marked target and destroy it.
Definition of antibody-dependent cellular cytotoxicity
Antibody-dependent cellular cytotoxicity is an immune killing mechanism in which antibodies coat a target cell and then act as handles for immune cells to grip. Natural killer cells lock onto the exposed tail of each bound antibody and release granules that punch holes in the target and drive it to die. The antibody marks; the cell does the killing.
How does the mechanism work step by step?
An antibody has two ends. The forked end recognizes and binds a specific target on the surface of an infected cell, a parasite or a tumor cell. The opposite end, called the Fc region, points outward once the antibody is attached. Natural killer cells carry receptors that grip that outward-facing end. When enough antibodies coat one target, the killer cell binds several at once, and that clustering is the signal it needs. It then releases perforin, which drills pores through the target membrane, and granzymes, enzymes that pass through those pores and instruct the cell to dismantle itself. The killer cell is unharmed and moves on to the next target.
How is it different from other ways of killing a cell?
| Mechanism | What marks the target | What does the killing |
|---|---|---|
| Antibody-dependent killing | Antibody coating the surface | Natural killer cell |
| Complement lysis | Antibody coating the surface | Blood proteins forming a pore |
| Cytotoxic T cell killing | Fragments displayed by the target | The T cell itself |
| Phagocytosis | Antibody or complement coating | A cell that engulfs the target |
Why does it matter for antibody drugs?
Many therapeutic antibodies depend on this mechanism for a large share of their effect. A monoclonal antibody aimed at a protein on a tumor cell may block a growth signal, but it also coats that cell and recruits natural killer cells to finish the work. Manufacturers alter the sugar groups attached to the Fc region to strengthen the recruitment, since small chemical changes there markedly improve the grip. Inherited differences in the Fc receptor also vary between people, and that variation appears to influence how well some forms of antibody therapy perform.
Where does it work against the body?
The same mechanism drives tissue damage in several autoimmune diseases. When antibodies form against a person's own cells, those cells are coated and destroyed in exactly the same way. Destruction of red cells and of platelets by this route causes anemia and low platelet counts, and it accounts for part of the damage seen in some thyroid and neuromuscular conditions.
Also known as
Used in a sentence
Laboratory testing measured antibody-dependent cellular cytotoxicity against the target cell line.
Good to know
Several therapeutic antibodies rely on this mechanism for much of their effect, so differences in a person's natural killer cell receptors can influence how well such a drug works.
Word origin
Where “antibody-dependent cellular cytotoxicity” comes from
Cytotoxicity comes from the Greek kytos, a hollow vessel and later a cell, with toxikon, meaning poison.