Human and murine monoclonal antibodies directed against a conserved sequence from gp41 (aa583–599) of human immunodeficiency virus type 1
Identifieur interne : 000384 ( France/Analysis ); précédent : 000383; suivant : 000385Human and murine monoclonal antibodies directed against a conserved sequence from gp41 (aa583–599) of human immunodeficiency virus type 1
Auteurs : A. Ebersold [France] ; V. Boyer [France] ; P. J. Klasse [Suède] ; M. Holnigue [France] ; C. Fraisier [France] ; J. M. Cocchi [France] ; R. Pipkorn [Allemagne] ; J. Blomberg [Suède] ; C. Desgranges [France]Source :
- Research in Virology [ 0923-2516 ] ; 1992.
English descriptors
- KwdEn :
- Teeft :
- Agence nationale, Assay, Biological activities, Colorimetric assay, Culture supernatants, Cytofluorimetric analysis, Elisa, Envelope glycoprotein, Epitope, Glycoprotein, Highest concentration, Hiv1, Hiv1 infection, Hivi, Hmab, Human immunodeficiency virus, Human immunodeficiency virus type, Hybrid growth, Immunization, Immunodeficiency, Immunosuppressive, Immunosuppressive effect, Klasse, Light chains, Lymphocyte, Mmab, Molt4 cells, Monoclonal antibody, Monoclonal humain, Negative control, Neutralization, Neutralization assays, Neutralizing, Neutralizing antibodies, Pbmc, Peptide, Peripheral blood, Phivis, Proliferation assay, Room temperature, Same region, Simian immunodeficiency virus, Single residues, Spleen, Spleen cells, Supernatant, Supt1 target cells, Supti target cells, Syncytia formation, Syncytium, Synthetic peptide, Target cells, Transmembrane protein, Uninfected supt1 target cells, Virol.
Abstract
Summary: Human spleen cells from an HIV-seropositive donor were immunized in vitro with the aa583–599 peptide conjugated to an heptalysyl core. This sequence was derived from the putatively HIV-immunosuppressive region of HIV1 gp41. The same conjugated peptide was used to immunize mice. One human and one mouse IgM monoclonal antibody (mAb) directed against the aa583–599 peptide were obtained. The two mAb had distinct patterns of reactivity against a panel of 42 peptides with modified sequences. Neither of the mAb inhibited the immunosuppressive effect of aa583–599 octopus-lysconjugated peptide on anti-CD3 Ab-induced lymphoproliferation. In addition, both mAb did not neutralize cell-free virus transmission or enhance HIV infection. However, HmAb inhibited formation of syncytia between HIV1-infected (but not HIV2-infected cells) and non-infected target cells at concentrations above 20 μg/ml, whereas MmAb did not have any effect. The degree of conservation of the aa583–599 region makes HmAb a candidate for use as a group-specific reagent in future HIV1 passive immunotherapy protocols.
Les lymphocytes de la rate d'un donneur séropositif pour le VIH ont été immunisés in vitro par un peptide synthétique constitué des acides aminés 583 à 599 de la région immunosuppressive de la gp41 du VIH. Pour l'immunisation, le peptide a été couplé à un «noyau heptalysine portant huit extrémités NH2-réactives. Ce même peptide a été injecté en parallèle à des souris. Un anticorps monoclonal humain et un anticorps monoclonal murin ont été obtenus. Tous deux d'isotype IgM, ils présentent une réactivité différente sur un groupe de 42 peptides présentant des modifications de séquence. Les deux anticorps n'inhibent pas les propriétés immunosuppressives du peptide 583–599 et ne neutralisent ni n'augmentent l'infection par du virus libre. Toutefois, l'anticorps monoclonal humain, et lui seul, présente la capacité d'inhiber la formation de syncytia entre des cellules infectées par différentes souches du VIH1 et des cellules cibles, cela à une concentration de 20 μg/ml. Le haut degré de conservation des acides aminés dans la région 583–599 fait de l'anticorps monoclonal humain un candidat éventuel pour des études d'immunothérapie passive.
Url:
DOI: 10.1016/S0923-2516(06)80102-0
Affiliations:
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Klasse</name><affiliation wicri:level="1"><country xml:lang="fr">Suède</country><wicri:regionArea>Section of Virology, Lund University</wicri:regionArea><wicri:noRegion>Lund University</wicri:noRegion></affiliation></author><author><name sortKey="Holnigue, M" sort="Holnigue, M" uniqKey="Holnigue M" first="M." last="Holnigue">M. Holnigue</name><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>Centre Régional de Transfusion sanguine</wicri:regionArea></affiliation></author><author><name sortKey="Fraisier, C" sort="Fraisier, C" uniqKey="Fraisier C" first="C." last="Fraisier">C. 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Pipkorn</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Novabiochem AG, Sandhausen</wicri:regionArea><wicri:noRegion>Sandhausen</wicri:noRegion><wicri:noRegion>Sandhausen</wicri:noRegion></affiliation></author><author><name sortKey="Blomberg, J" sort="Blomberg, J" uniqKey="Blomberg J" first="J." last="Blomberg">J. Blomberg</name><affiliation wicri:level="1"><country xml:lang="fr">Suède</country><wicri:regionArea>Section of Virology, Lund University</wicri:regionArea><wicri:noRegion>Lund University</wicri:noRegion></affiliation></author><author><name sortKey="Desgranges, C" sort="Desgranges, C" uniqKey="Desgranges C" first="C." last="Desgranges">C. Desgranges</name><affiliation wicri:level="1"><country xml:lang="fr">France</country><wicri:regionArea>Unité de Recherche sur les Hépatites, le SIDA et les Rétrovirus humains, INSERM U271, 151 Cours Albert Thomas</wicri:regionArea><wicri:noRegion>151 Cours Albert Thomas</wicri:noRegion><wicri:noRegion>151 Cours Albert Thomas</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Research in Virology</title><title level="j" type="abbrev">X135</title><idno type="ISSN">0923-2516</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1992">1992</date><biblScope unit="volume">143</biblScope><biblScope unit="supplement">C</biblScope><biblScope unit="page" from="179">179</biblScope><biblScope unit="page" to="191">191</biblScope></imprint><idno type="ISSN">0923-2516</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0923-2516</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Lymphocyte, Peptide, HIV, AIDS, mAb, IgM, Immunotherapy</term><term>gp41, Immunosuppression, Syncytia, pHIVIS, Heptalysine</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Agence nationale</term><term>Assay</term><term>Biological activities</term><term>Colorimetric assay</term><term>Culture supernatants</term><term>Cytofluorimetric analysis</term><term>Elisa</term><term>Envelope glycoprotein</term><term>Epitope</term><term>Glycoprotein</term><term>Highest concentration</term><term>Hiv1</term><term>Hiv1 infection</term><term>Hivi</term><term>Hmab</term><term>Human immunodeficiency virus</term><term>Human immunodeficiency virus type</term><term>Hybrid growth</term><term>Immunization</term><term>Immunodeficiency</term><term>Immunosuppressive</term><term>Immunosuppressive effect</term><term>Klasse</term><term>Light chains</term><term>Lymphocyte</term><term>Mmab</term><term>Molt4 cells</term><term>Monoclonal antibody</term><term>Monoclonal humain</term><term>Negative control</term><term>Neutralization</term><term>Neutralization assays</term><term>Neutralizing</term><term>Neutralizing antibodies</term><term>Pbmc</term><term>Peptide</term><term>Peripheral blood</term><term>Phivis</term><term>Proliferation assay</term><term>Room temperature</term><term>Same region</term><term>Simian immunodeficiency virus</term><term>Single residues</term><term>Spleen</term><term>Spleen cells</term><term>Supernatant</term><term>Supt1 target cells</term><term>Supti target cells</term><term>Syncytia formation</term><term>Syncytium</term><term>Synthetic peptide</term><term>Target cells</term><term>Transmembrane protein</term><term>Uninfected supt1 target cells</term><term>Virol</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Summary: Human spleen cells from an HIV-seropositive donor were immunized in vitro with the aa583–599 peptide conjugated to an heptalysyl core. This sequence was derived from the putatively HIV-immunosuppressive region of HIV1 gp41. The same conjugated peptide was used to immunize mice. One human and one mouse IgM monoclonal antibody (mAb) directed against the aa583–599 peptide were obtained. The two mAb had distinct patterns of reactivity against a panel of 42 peptides with modified sequences. Neither of the mAb inhibited the immunosuppressive effect of aa583–599 octopus-lysconjugated peptide on anti-CD3 Ab-induced lymphoproliferation. In addition, both mAb did not neutralize cell-free virus transmission or enhance HIV infection. However, HmAb inhibited formation of syncytia between HIV1-infected (but not HIV2-infected cells) and non-infected target cells at concentrations above 20 μg/ml, whereas MmAb did not have any effect. The degree of conservation of the aa583–599 region makes HmAb a candidate for use as a group-specific reagent in future HIV1 passive immunotherapy protocols.</div><div type="abstract" xml:lang="fr">Les lymphocytes de la rate d'un donneur séropositif pour le VIH ont été immunisés in vitro par un peptide synthétique constitué des acides aminés 583 à 599 de la région immunosuppressive de la gp41 du VIH. Pour l'immunisation, le peptide a été couplé à un «noyau heptalysine portant huit extrémités NH2-réactives. Ce même peptide a été injecté en parallèle à des souris. Un anticorps monoclonal humain et un anticorps monoclonal murin ont été obtenus. Tous deux d'isotype IgM, ils présentent une réactivité différente sur un groupe de 42 peptides présentant des modifications de séquence. Les deux anticorps n'inhibent pas les propriétés immunosuppressives du peptide 583–599 et ne neutralisent ni n'augmentent l'infection par du virus libre. Toutefois, l'anticorps monoclonal humain, et lui seul, présente la capacité d'inhiber la formation de syncytia entre des cellules infectées par différentes souches du VIH1 et des cellules cibles, cela à une concentration de 20 μg/ml. Le haut degré de conservation des acides aminés dans la région 583–599 fait de l'anticorps monoclonal humain un candidat éventuel pour des études d'immunothérapie passive.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>France</li><li>Suède</li></country></list><tree><country name="France"><noRegion><name sortKey="Ebersold, A" sort="Ebersold, A" uniqKey="Ebersold A" first="A." last="Ebersold">A. Ebersold</name></noRegion><name sortKey="Boyer, V" sort="Boyer, V" uniqKey="Boyer V" first="V." last="Boyer">V. Boyer</name><name sortKey="Cocchi, J M" sort="Cocchi, J M" uniqKey="Cocchi J" first="J. M." last="Cocchi">J. M. Cocchi</name><name sortKey="Desgranges, C" sort="Desgranges, C" uniqKey="Desgranges C" first="C." last="Desgranges">C. Desgranges</name><name sortKey="Fraisier, C" sort="Fraisier, C" uniqKey="Fraisier C" first="C." last="Fraisier">C. Fraisier</name><name sortKey="Holnigue, M" sort="Holnigue, M" uniqKey="Holnigue M" first="M." last="Holnigue">M. Holnigue</name></country><country name="Suède"><noRegion><name sortKey="Klasse, P J" sort="Klasse, P J" uniqKey="Klasse P" first="P. J." last="Klasse">P. J. Klasse</name></noRegion><name sortKey="Blomberg, J" sort="Blomberg, J" uniqKey="Blomberg J" first="J." last="Blomberg">J. Blomberg</name></country><country name="Allemagne"><noRegion><name sortKey="Pipkorn, R" sort="Pipkorn, R" uniqKey="Pipkorn R" first="R." last="Pipkorn">R. Pipkorn</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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