Antigenic complementarity among AIDS-associated infectious agents and molecular mimicry of lymphocyte proteins as inducers of lymphocytotoxic antibodies and circulating immune complexes

Background: People at risk for acquired immunodeficiency syndrome (AIDS) have high rates of cofactor infections in addition to HIV, including cytomegalovirus, hepatitis viruses, Mycobacteria, Mycoplasmas, and Staphylococcus aureus. Most people with AIDS also develop lymphocytotoxic antibodies (LCTA) and circulating immune complexes (CIC). While HIV proteins mimic HLA antigens, many cofactor agents mimic CD4 antigens. It has therefore been proposed that cofactor infections may interact with HIV by producing complementary antigens that induce LCTA and CIC, and that the resulting immunological dysfunction is part of AIDS pathogenesis. Objectives: To test (1) whether HIV and its cofactor infections elicit complementary (idiotype-anti-idiotype) antibodies, and (2) if any of these antibodies mimic anti-lymphocyte antibodies. Study design: Two immunological methods are employed to test for antibody complementarity: (1) double antibody diffusion, a modification of Ouchterlony immunodiffusion, in which antibodies are tested for their ability to precipitate each other; (2) double-antibody ELISA, in which an antibody against one infectious agent is adsorbed to an ELISA plate and an antibody against a second agent is used to detect the first. Results: Data on over a thousand double antibody diffusion (DAD) and about 70 DA-ELISA experiments are reported. These show that only specific pairs of antibodies are complementary: HIV-CMV; HIV-HBV; HIV-tuberculosis; HIV-mycoplasmas; HIV-S. aureus; and CMV-mycoplasmas. In addition, HIV antibodies precipitate CD4 antibodies; CMV antibodies precipitate HLA-DR antibodies; while mycobacteria and mycoplasma antibodies precipitate macrophage antibodies. Conclusions: Antibodies elicited by HIV infection can interact with antibodies elicited by cofactor infections to form CIC, and some of these antibodies mimic lymphocyte antibodies so that they may function as LCTA. Since LCTA and CIC are associated with increased lymphocyte death in AIDS, the immune response against cofactors in HIV may play a significant role in AIDS pathogenesis. The fact that both HIV and cofactors elicit antibodies with LCTA characteristics may pose problems for vaccine development. (C) 2004 Elsevier B.V. All rights reserved.