IgM natural antibody against an asialooligosaccharide, gangliotetraose (Gg4), sensitizes HIV-I infected cells for cytolysis by homologous complement

Abstract

Although cells are usually resistant to homologous complement, the IgM natural antibody against gangliotetraose (Gg4), an asialo-oligosaccharide of GM1, was found to cause cytolysis of HIV-1 infected cells by homologous complement. Due to its size, IgM might enable the initiation of the complement cascade away from membrane complement inhibitors such as decay accelerating factor and membrane cofactor protein. Furthermore, HRF20 (CD59), which restricts formation of membrane attack complexes (MAC) of complement on homologous cell membranes, was significantly decreased on HIV-infected cells and therefore formation of MAC on cell membranes would be facilitated. IgM antibodies reactive with HIV-infected cells could result in the elimination of infected cells via complement-mediated cytolysis in HIV-infected patients, since all tested sera from HIV-positive hemophilia patients who have survived for > 12 years contained IgM antibody activity against HIV-infected MOLT4 cells in a preliminary experiment. Therefore, administration of IgM antibodies reactive with HIV-infected cells may be effective in the treatment of HIV carriers.