Cross-reactivity of anti-human immunodeficiency virus type 1 gp41 antibodies with human astrocytes and astrocytoma cell lines.
An antigen expressed by astrocytes in human brain tissue and by various human astrocytoma cell lines was shown to cross-react with a monoclonal antibody generated against amino acids (aa) 584 to 609 of the transmembrane protein gp41 of human immunodeficiency virus type 1 (HIV-1). This region is an immunodominant segment of gp41, and high levels of antibodies against this epitope have been detected in both serum and cerebrospinal fluid of HIV-infected individuals at all stages of HIV infection. Immunohistochemistry with this monoclonal antibody demonstrated the presence of a cross-reactive antigen in human brain tissue, with an increased frequency and intensity of staining in HIV-positive individuals when compared with HIV-negative controls. By using a panel of HIV-positive and -negative sera, we show that antibodies in HIV-positive serum specifically bound to the surfaces of human astrocytoma cells. HIV-positive sera depleted of antibodies recognizing gp41 aa 584 to 609 showed a significant diminution in cell surface binding. Conversely, the serum antibodies that bound to and were eluted from the aa 584 to 609 peptide also bound to the astrocyte cell surface. To identify the target antigen, the immunoreactivity of three astrocytoma cell lines was examined. By immunoprecipitation of metabolically labeled cell lysates and Western blot (immunoblot) analysis, we identified a protein of approximately 100 kDa as the target antigen. Cross-reactive antibodies between HIV proteins and astrocyte epitopes, such as this 100-kDa protein and others previously reported, suggests that an autoimmune response against these target antigens may disrupt the normal functions of astrocytes.
Spehar
T
T
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Strand
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M
D015526:AIDS Dementia Complex / Q000473:pathology*; D000163:Acquired Immunodeficiency Syndrome / Q000473:pathology*; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000032:analysis*; D001253:Astrocytes / Q000166:cytology / Q000473:pathology*; D001254:Astrocytoma / Q000473:pathology*; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000473:pathology*; D002460:Cell Line; D003429:Cross Reactions; D015686:Gene Products, env / Q000032:analysis / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41 / Q000032:analysis* / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000032:analysis / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015686:Gene Products, env; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D011498:Protein Precursors; D011994:Recombinant Proteins