Anti-GP 120 antibodies from HIV seropositive individuals mediate broadly reactive anti-HIV ADCC.

Cytophilic antibodies which mediate antibody dependent cellular cytotoxicity (ADCC) against envelope antigens of human immunodeficiency virus (HIV) can be found in seropositive individuals. In these experiments, sera from a wide spectrum of HIV infected patients ranging from asymptomatic to overt acquired immunodeficiency syndrome (AIDS) were shown to contain high titers of antibodies that mediate ADCC. Not only did patient antibodies bind to surface expressed viral antigens and mediate ADCC against cells chronically infected with human T-lymphotropic virus type IIIB (HTLV-IIIB), but also against cells infected with the divergent HTLV-IIIRF2 and HTLV-IIIMN viral isolates. Similar results were obtained with target cells bearing purified GP 120 from HTLV-IIIB and HTLV-IIIRF2, indicating that a major portion of the activity was mediated by anti-GP 120 antibodies. Consistent with this was the ability to absorb most of the group-specific ADCC activity from the serum of an HIV infected individual using affinity columns bearing purified HTLV-IIIB GP 120. The finding that human antibodies reactive against the HIV envelope glycoprotein mediate ADCC against cells chronically infected with divergent strains of HIV will have important implications in designing rational approaches to passive and active immunotherapy.

[1]  A J Langlois,et al.  Human T-cell lymphotropic virus IIIB glycoprotein (gp120) bound to CD4 determinants on normal lymphocytes and expressed by infected cells serves as target for immune attack. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[2]  R. Snyderman,et al.  A conserved region at the COOH terminus of human immunodeficiency virus gp120 envelope protein contains an immunodominant epitope. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Malcolm Rees,et al.  The sombre view of AIDS , 1987, Nature.

[4]  Roy M. Anderson,et al.  Transmission dynamics of HIV infection , 1987, Nature.

[5]  P. Kourilsky,et al.  Retrovirus antigens recognized by cytolytic T lymphocytes activate tumor rejection in vivo , 1987, Cell.

[6]  A J Langlois,et al.  HTLV-III/LAV-neutralizing antibodies to an E. coli-produced fragment of the virus envelope. , 1986, Science.

[7]  R. Gallo,et al.  Restricted neutralization of divergent human T-lymphotropic virus type III isolates by antibodies to the major envelope glycoprotein. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[8]  L. Arthur,et al.  Prospect for prevention of human immunodeficiency virus infection: purified 120-kDa envelope glycoprotein induces neutralizing antibody. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[9]  D. Markovitz,et al.  The role of mononuclear phagocytes in HTLV-III/LAV infection. , 1986, Science.

[10]  J. Mcdougal,et al.  In vitro infection of human monocytes with human T lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). , 1986, Journal of immunology.

[11]  Hans Wolf,et al.  Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS , 1986, Cell.

[12]  K. Lui,et al.  A model-based approach for estimating the mean incubation period of transfusion-associated acquired immunodeficiency syndrome. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[13]  P. Cresswell,et al.  Natural killing target antigens as inducers of interferon: studies with an immunoselected, natural killing-resistant human T lymphoblastoid cell line. , 1985, Journal of immunology.

[14]  M. Popovič,et al.  T4 POSITIVE HUMAN NEOPLASTIC CELL LINES SUSCEPTIBLE TO AND PERMISSIVE FOR HTLV-III , 1984, The Lancet.

[15]  J. Levy,et al.  Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. , 1984, Science.

[16]  F. Brun-Vézinet,et al.  DETECTION OF IgG ANTIBODIES TO LYMPHADENOPATHY-ASSOCIATED VIRUS IN PATIENTS WITH AIDS OR LYMPHADENOPATHY SYNDROME , 1984, The Lancet.

[17]  B. Haynes,et al.  Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. , 1984, Science.

[18]  R. Gallo,et al.  Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. , 1984, Science.

[19]  J Schüpbach,et al.  Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS. , 1984, Science.

[20]  J. Ihle,et al.  Properties of mouse leukemia viruses. XIX. Effective antibody therapy of AKR leukemia occurs independently of virus neutralization and produces long-term changes in the virus status of the thymus. , 1984, Virology.

[21]  T. Aoki,et al.  In vitro antibody‐dependent cellular cytotoxicity against human T‐cell leukemia/lymphoma virus (HTLV)‐producing cells , 1984, International journal of cancer.

[22]  J. Chermann,et al.  Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). , 1983, Science.

[23]  D. Tribe,et al.  Analysis of human serum antibodies to human immunodeficiency virus (HIV) using recombinant ENV and GAG antigens. , 1987, AIDS research and human retroviruses.

[24]  Luc Montagnier,et al.  T-lymphocyte T4 molecule behaves as the receptor for human retrovirus  LAV , 1984, Nature.