HIV-1-Specific Antibody-Dependent Cellular Cytotoxicity (ADCC)

Antibodies elicited during the course of HIV-1 infection can act as a bridge between cytolytic cells and HIV-1-infected cells or other cells that have passively absorbed appropriate HIV-1-antigens. These cytolytic cells cause lysis of the HIV-1-infected cells thereby decreasing viral load (1 –5 ) . The effector cells for ADCC are natural killer (NK) cells, that mediate lysis in a non-MHC restricted fashion. NK cells expressing CD16⁺ low affinity Fc-receptors bind to antibody which specifically binds to the antigen expressed on target cells. Two types of ADCC activity can be demonstrated in HIV-1-infected patients. The first type, the classical or indirect ADCC, is assayed using normal donor lymphocytes and HIV-1 patient sera. Lysis of HIV-1 envelope protein-coated or HIV-1-infected target cells is detected in a chromium 51 [⁵¹ Cr] release assay. Sera from HIV-1-infected individuals appear to mediate indirect ADCC regardless of their disease status. A second type, or direct ADCC, uses NK cells freshly isolated from HIV-1-infected individuals. These NK cells are coated with anti-HIV-1 cytophilic antibodies and can readily lyse envelope-coated or HIV-1-infected target cells. The latter may be a more pertinent measure of ADCC activity since the activity of this type of NK-mediated ADCC declines as HIV-1 disease progresses (6 ).