Distribution and antigenic analysis of circulating F(ab')2-reactive IgG in patients with HIV-1 infection.

Serum titers and molecular specificity of anti-F(ab')2 antibodies were investigated in human immunodeficiency virus type 1 (HIV-1) infection with respect to their supposed cytopenic role on CD4+ cells. The levels of antibodies to F(ab')2 fragment and to HIV-1 glycoprotein epitopes were measured by immunoenzymatic methods in an HIV-1+ population, including 86 drug addicts, 12 sexually infected patients, and 1 hemophiliac, grouped into Walter Reed (WR) clinical stages 2 to 6 of HIV-1 infection. Monoclonal F(ab')2-reactive IgM and IgG from cloned Epstein-Barr B cell transformants of selected patients were also investigated in regards to their HIV-1 glycoprotein specificities and cytotoxicity to the CD4+ cell membrane antigens (CEM) lymphoblasts by a Terasaki assay. Group A (51 sera from WR2 patients) showed the highest titers of IgG anti-F(ab')2 with no correlation to positivities to gp120, whereas sera with undetectable anti-F(ab')2 levels from group B (37 WR5 and WR6 patients) and from group C (11 WR3-WR6 patients with lymphocytotoxin-associated lymphopenia) were reactive to the virus envelope. Both anti-F(ab')2 monoclonal IgM and IgG failed to cross-react with the HIV-1 glycoproteins and the CD4+ CEM. Based on our data, anti-F(ab')2 antibodies are apparently unrelated to the CD4+ lymphopenia occurring in HIV-1-infection. In addition, their inability to bind the HIV-1 gp120 as sequence homologue of the CH1 domain of IgG suggests that their molecular target could include a few epitopes located within the VH and VL regions, thus supporting their potential role of antiidiotype molecules as described in autoimmunity.