COMPLEMENT-ACTIVATING ANTIBODIES IN SERA FROM INFECTED INDIVIDUALS AND VACCINATED VOLUNTEERS THAT TARGET HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TO COMPLEMENT RECEPTOR-TYPE-1 (CR-1, CD35)

Complement receptor type 1 (CR1) plays a central role in clearing immu ne complexes from the circulation and probably contributes to the rete ntion of immune complexes on the surface of follicular dendritic cells . Virus-specific, complement-activating antibodies can target human im munodeficiency virus type 1 (HIV-1) to CR1-bearing cells but the poten tial impact that these antibodies have on HIV-1 pathogenesis is unknow n. To study these antibodies, an assay was developed in which immune c omplexes containing HIV-1, antibody, and complement were formed in vit ro and captured on the surface of 96-well immunoplates coated with rec ombinant soluble human CR1 (rsCR1). Captured virus was detected by p24 immunoassay or by infection of human CD4(+) lymphocytes. Two laborato ry strains of HIV-1 (IIIB and MN) and primary isolates could be captur ed using sera from infected individuals or vaccinated volunteers as a source of complement-activating antibodies. HIV-1 immune complexes cap tured by solid-phase rsCR1 could be transferred to MT-2 cells for prod uctive infection. Antibodies had no activity in this assay when the no rmal human serum used as a source of complement had been heat-inactiva ted or depleted of complement component C3, confirming a requirement f or complement. These complement-activating antibodies in sera from inf ected individuals showed strong cross-reactivity with HIV-1 IIIB, MN, and a heterologous primary isolate, but reacted poorly with the autolo gous isolate obtained at the time of serum collection. Average titers of these antibodies measured with HIV-1 IIIB were moderately lower in HIV-1-infected progressors compared to nonprogressors. In contrast to sere from infected individuals, sera from gp160(IIIB)-vaccinated volun teers showed specificity for the vaccine strain or virus. These result s provide supporting evidence that envelope-specific, complement-activ ating antibodies induced by infection or gp160 immunization can target HIV-1 immune complexes to CR1. In addition, they demonstrate that suc h antibodies may sometimes be type-specific and that HIV-1 immune comp lexes bound to CR1 are infectious. (C) 1996 Academic Press, Inc.