Characterization and large production of human monoclonal antibodies against the HIV-1 envelope

Boyer, Véronique; Broly, Hervé; Souche, Sylvie; Madaule, Pascal; Rossier, Jean; Zagury, Daniel; Des̀granges, Claude

doi:10.1111/j.1365-2249.1991.tb05660.x

Cited by 12 publications

(1 citation statement)

References 37 publications

(24 reference statements)

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“…In addition, the high background production of anti-viral antibodies makes selection of specific EBV lines very difficult, as many apparently positive cultures prove to be negative on subsequent transfer and re-test. In one case peripheral blood lymphocytes were obtained from a volunteer deliberately immunized with a vaccinia virus recombinant expressing gpl60 [175,177,181]. Interestingly, the hMoAbs produced were specific for the gp4l portion of the immunizing molecule.…”

Section: Source Of Immune Lymphocytesmentioning

confidence: 99%

B cell responses to HIV and the development of human monoclonal antibodies

Boyd

James

1992

Clinical and Experimental Immunology

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SUMMARYIn this review B cell responses in HIV-infected individuals are summarized together with the techniques used to date to produce human monoclonals to HIV and the properties of these antibodies. Profound disturbances in B cell responses are apparent both in vivo and in vitro. While there is evidence in vivo of marked polyclonal B cell activation, primary and secondary antibody responses are impaired. Similarly these cells exhibit spontaneous immunoglobulin secretion upon in vitro culture but do not readily respond to B cell mitogens and recall antigens including HIV. Furthermore, certain of these defects can be reproduced in normal B cells in vitro by incubation with HIV or HIV coded peptides. Individuals infected with HIV develop antibodies to HIV structural proteins (e.g. pl7, p24, gp41 and gpl20) and regulatory proteins (e.g. vif, nef, RT). Autoantibodies against a number of immunologically important molecules are also frequently observed. The anti-HIV antibodies are predominantly ofthe IgGl isotype and exhibit a variety of effects on the virus in vitro. To date, using conventional immortalization strategies, an appreciable number of human monoclonals to HIV have been developed. These have been specific for gp41, gpl20 and gag with antibodies ofthe former specificity predominating. The majority of these antibodies have been ofthe IgGl isotype. Only a small number ofthe antibodies neutralize virus in vitro and most of these react with gpl20. The neutralizing antibodies recognize conformational and carbohydrate epitopes or epitopes in amino acid positions 306-322. The predominant epitopes recognized by the anti-gp41 antibodies were in amino acid positions 579-620 and 644-662. A high percentage (=^ 25%) of these antibodies enhance viral growth in vitro. The problems relating to the production of human monoclonals to HIV are discussed together with strategies that could be used in the future.

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Section: Source Of Immune Lymphocytesmentioning

confidence: 99%

B cell responses to HIV and the development of human monoclonal antibodies

Boyd

James

1992

Clinical and Experimental Immunology

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Comparison of the antibody response to bee venom phospholipase A2 induced by natural exposure in humans or by immunization in mice

Schneider¹,

Dudler²,

Annand

et al. 1997

J. Mol. Recognit.

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Two human and twelve murine monoclonal antibodies directed against the main bee venom allergen phospholipase A2 (PLA) were evaluated for their fine specificity of binding to antigen and their ability to inhibit the enzymatic activity of the antigen. Antibodies were induced by natural exposure of beekeepers to bee venom or immunization of mice via different methods. Both human monoclonal antibodies (hmAbs) were previously shown to recognize the native three-dimensional conformation of PLA and are directed against discontinuous epitopes which include lysine residue at position 25 as a contact residue. In contrast, six of the murine monoclonal antibodies (mmAbs) bind to the denatured structure of the protein as determined by enzyme-linked immunosorbent assay. The epitopes recognized are located near the C-terminal end (n = 8), in the centre of the polypeptide (n = 1), near the N-terminal end (n = 1) or include the carbohydrate part (n = 2) of the PLA molecule. The capacity of the antibodies to modify the enzymatic activity was also determined. The hmAbs significantly inhibit the enzyme (70-79%), whereas the mmAbs produced various degrees of inhibition (39-100%). Since the X-ray structure of PLA is known, the epitopes can be visualized in the context of the three-dimensional structure of the antigen. A qualitative correlation was found between the location of epitopes and the inhibition pattern. Strong inhibition was seen with those antibodies that recognize epitopes that lie on the surface of the enzyme that is thought to contact the phospholipid bilayer. The results show that even though both hmAbs and most mmAbs inhibit the enzymatic activity of PLA, the antigen-binding properties of antibodies from different species raised after different routes of immunization differ significantly. Thus, detailed epitope mapping studies using murine antibodies prepared by artificial immunization may have limited value in predicting epitope patterns relevant to an antibody response to allergens in humans naturally exposed to antigen/allergen.

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Characterization of Human Monoclonal Antibodies Specific to the Hepatitis C Virus Glycoprotein E2 within VitroBinding Neutralization Properties

Habersetzer¹,

Fournillier²,

Dubuisson

et al. 1998

Virology

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Both linear and conformational determinants of hepatitis C virus (HCV) are believed to be involved in viral neutralization. After immortalization of B cells from HCV chronically infected patients with Epstein-Barr virus, we obtained two polyclonal lymphoblastoid cell lines (LCL) secreting human monoclonal antibodies (HMabs). One clone was derived from a patient infected with a genotype 4 isolate while the second was isolated from a genotype 1b-infected patient. Immunoprecipitation studies, Western blot, and immunofluorescence analysis, peptide scanning, and ELISA studies indicated that the HMabs (1) recognized conformation-dependent determinant(s), (2) were capable of recognizing genotype 1a and 1b derived antigens, and (3) were able to precipitate noncovalently associated E1E2 complexes believed to exist on the surface of virion particles. The HMab derived from the genotype 4-infected patient was in addition shown to neutralize the in vitro binding of recombinant E2 protein onto susceptible cells suggesting a potential for in vivo neutralization. These data indicate that anti-E2 antibodies directed at conserved conformational-dependent determinant(s) exist in chronic HCV infection.

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Characterization and large production of human monoclonal antibodies against the HIV-1 envelope

Cited by 12 publications

References 37 publications

B cell responses to HIV and the development of human monoclonal antibodies

B cell responses to HIV and the development of human monoclonal antibodies

Comparison of the antibody response to bee venom phospholipase A2 induced by natural exposure in humans or by immunization in mice

Characterization of Human Monoclonal Antibodies Specific to the Hepatitis C Virus Glycoprotein E2 within VitroBinding Neutralization Properties

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