Document 1884 DOCN M94A1884 TI Molecular mimicry between V3 loop of HIV-1 gp120 and endogenous human proteins. DT 9412 AU Trujillo JR; McLane MF; Lee TH; Essex M; Harvard School of Public Health, Cancer Bio. Dept., Boston, MA. SO Int Conf AIDS. 1994 Aug 7-12;10(1):43 (abstract no. 144A). Unique Identifier : AIDSLINE ICA10/94370691 AB OBJECTIVE: Viral infections can induce autoimmune responses by several mechanisms including molecular mimicry. To determine the role of the cellular immune response in HIV pathogenesis, antibodies to gp120, a highly immunogenic protein of HIV-1, were analyzed for cross-reactivity with endogenous human proteins. METHODS AND RESULTS: Homogenized brain, kidney, liver, lung and spleen tissues from HIV-1 seronegative individuals as well as lysates from various cell lines were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Initial western blot analyses of human brain proteins (HBP) with several monoclonal and polyclonal anti-HIV-1 antibodies including anti-HIV-1 gp120, anti-gp120 V3 loop (V3mAb), anti-gp120 V5 loop, anti-gp41, anti-p24, anti-p17, anti-Vpu and anti-Vpr revealed cross-reactivity only with the V3mAb. The V3mAb specifically reacted with three prominent human brain proteins of approximately 35, 55 and 110 kDa and with minor proteins of 23 and 65 kDa. The 55 kDa human brain protein appears to be specific to the central nervous system. Western blot analyses of proteins from peripheral tissues and various cell lines were performed using the V3mAb and revealed reactivity to 35 and 110 kDa proteins. Binding of the V3mAb to endogenous human proteins appears to be specific since it was competitively blocked by recombinant HIV-1 gp120. DISCUSSION AND CONCLUSIONS: The V3 loop of HIV-1 gp120 appears to share an epitope with endogenous human proteins. An immune response to the V3 loop that can generate cross-reactive antibodies to cellular proteins may be an autoimmune mechanism by which HIV-1 can damage cells within the central nervous system and other organs. DE Antibodies, Monoclonal Antigenic Determinants/IMMUNOLOGY/ISOLATION & PURIF Autoantibodies/BIOSYNTHESIS Autoantigens/ISOLATION & PURIF Binding, Competitive Brain/IMMUNOLOGY Cell Line Cross Reactions Human HIV Antibodies HIV Antigens HIV Envelope Protein gp120/*IMMUNOLOGY HIV Infections/IMMUNOLOGY HIV-1/*IMMUNOLOGY Immunity, Cellular Molecular Weight Nerve Tissue Proteins/CHEMISTRY/IMMUNOLOGY Peptide Fragments/*IMMUNOLOGY Proteins/*IMMUNOLOGY/ISOLATION & PURIF MEETING ABSTRACT SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).