The chimeric mouse-human anti-CD4 Fab 13B8.2 expressed in baculovirus inhibits both antigen presentation and HIV-1 promoter activation
| Autor: | Jean-Claude Mani, Bernard Pau, Thierry Chardès, Sylvie Peraldi-Roux, Gérard Devauchelle, Christian Devaux, Cédric Bès, Martine Pugnière, Damien Bresson, Martine Cerutti, Laurence Briant-Longuet, Claude Granier |
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| Přispěvatelé: | Biologie Intégrative et Virologie des Insectes [Univ. de Montpellier II] (BIVI), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2) |
| Rok vydání: | 2001 |
| Předmět: |
HIV Antigens
medicine.drug_class Recombinant Fusion Proteins [SDV]Life Sciences [q-bio] T cell Molecular Sequence Data Immunology Antigen presentation Enzyme-Linked Immunosorbent Assay Biology Humanized antibody Immunoglobulin light chain Monoclonal antibody law.invention Epitopes Immunoglobulin Fab Fragments Mice 03 medical and health sciences 0302 clinical medicine law Gene expression medicine Animals Humans Immunology and Allergy Amino Acid Sequence Promoter Regions Genetic 030304 developmental biology 0303 health sciences Antibodies Monoclonal HIV General Medicine Molecular biology 3. Good health medicine.anatomical_structure Cell culture 030220 oncology & carcinogenesis CD4 Antigens HIV-1 Recombinant DNA Virus Activation Baculoviridae |
| Zdroj: | Human Antibodies Human Antibodies, IOS Press, 2001, 10, pp.67-76 Europe PubMed Central ResearcherID |
| ISSN: | 1875-869X 1093-2607 |
| Popis: | The anti-CD4 mAb 13B8.2, directed against the CDR3-like loop of the D1 domain of CD4, inhibits signal transduction pathways leading to both T cell activation and HIV replication. VH9/DSP2/JH2 and Vkappa12-13/Jkappa2 rearrangements, corresponding to genes encoding the heavy and light chain variable regions of the 13B8.2 mAb, were inserted into baculovirus cassettes upstream from pre-installed human Fdgamma1 and Ckappa genes, respectively. After expression in insect cells, a complete correctly-processed Fab was secreted into the culture medium; it was protein-G immunopurified with a yield of 5 mg/L. The chimeric Fab 13B8.2 showed anti-CD4 binding activity with an affinity value of 3.3 nM and recognized the same region on the CDR3-like loop as the parental mAb. The mouse-human Fab inhibited IL2 secretion following antigen presentation and displayed a strong capacity to prevent HIV-1 promoter activation. Taken together, these results indicate that the chimeric Fab retained a major part of the parental 13B8.2 mAb properties and suggest that it might be a valuable therapeutic tool. |
| Databáze: | OpenAIRE |
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