A human anti-HIV autoantibody enhances EBV transformation and HIV infection

A highly specific, human IgG mAb, F223, which reacts with both HIV-1-infect ed cells and uninfected lymphoid cells, has been derived. F223 reacts with gp120 but fails to neutralize viral infection. The antibody does enhance HI IV-1 infection in a complement-dependent manner. The autoantigen recognized by F223 is expressed on a small percentage of T cells and NK cells and the majority of B cells. Immunoprecipitation demonstrates F223 reactivity with an as of yet unidentified 159-kDa protein in uninfected lymphoid cells. Th is reactivity with uninfected cells is inhibited by free gp120 demonstratin g the cross-reactive nature of this antibody. The F223 light chain demonstr ates strong homology to VL lambda 2 family genes whereas the heavy chain is most homologous (84%) to the germline gene VH3-H.11. In vivo usage of VH3 family genes by F223 and an anti-HN-l (gp41) human mAb, 3D6, with related a utoreactivity, suggests that VH3 sequences may be important components of p otentially pathogenic human anti-HIV-1 envelope autoantibodies. F223 was is olated from an HIV-1 infected individual with lymphoma and in vitro F223 si gnificantly enhances EBV transformation of normal B cells and increases imm unoglobulin production without affecting B cell proliferation. Characteriza tion of this antibody response may provide important insights and mechanist ic information on HIV pathogenesis. (C) 1999 Academic Press.