Complement enhances antiviral antibody-dependent cell cytotoxicity

Abstract

ANTIBODY-DEPENDENT cell cytotoxicity (ADCC) is an in vitro phenomenon that can be demonstrated with a variety of target cell systems and can be mediated by several types of effector cells^1–3. The effectors in ADCC must bear a surface receptor for Fc, and this receptor binds with antibody which is in turn bound to the target cell. Only certain classes and subclasses of immunoglobulins can sensitise cells for ADCC^4,5. Although the presence of a Fc receptor is necessary for ADCC, it is not sufficient since cells bearing such receptors may fail to mediate ADCC against a particular target^1–3,6,7. Similarly, union of effectors with targets by means of a different receptor such as the complement receptor may not result in cytotoxicity^8,9. Whether the efficiency of different cells at mediating ADCC depends on the number, type or affinity of Fc receptors, whether a cooperation between different types of surface receptors is needed¹⁰ or whether some property of the target cells decides the outcome of contact between effectors and targets, has not been established. It is likely that ADCC occurs only if a sufficient union is established between effector and target cell. Such a union could be generated by bonds between the target cell and two types of surface receptors on the effectors—such as the Fc receptor and the complement receptor, both of which are present on effector cells^10–12. Using herpes-virus infected target cells we here provide support for this hypothesis and show that the addition of complement, at levels below those required for antibody–complement lysis, considerably enhances ADCC and, furthermore, permits cells to mediate ADCC that in the absence of complement could not do so.