COMPLEMENT ACTIVATION BY RECOMBINANT HIV-1 GLYCOPROTEIN GP120

The mechanism of CD4(+) cell depletion in HIV-infected patients is poo rly understood. In this study we investigated whether rgp120 can activ ate the complement system in the absence of anti-gp120 Abs. We found t hat the complement proteins C4, C3d, C5b-9, and properdin bind to rgp1 20-coated CD4(+) T cells of healthy individuals when incubated in auto logous serum. Activation of the complement system occurred primarily v ia the classical pathway and was abolished in sera deficient in C1q an d C4 as well as in the presence of EDTA. No cell lysis was observed in a lymphocytotoxicity assay using human serum, possibly because of hom ologous restriction of complement lysis. In contrast, addition of rabb it sera induced lysis of the rgp120-precoated cells. Cell lysis by rab bit serum was found to be because of naturally occurring IgM anti-gp12 0 Abs. The rgp120, which was immobilized on the surface of microtiter plates activated complement in the absence of lymphocytes. Complement activation by cell-bound HIV-1 envelope glycoprotein gp120 with subseq uent opsonization may be relevant for the elimination of noninfected C D4(+) T cells in HIV-infected patients.