Neutralization of Human Interleukin 23 by Multivalent Nanobodies Explained by the Structure of Cytokine–Nanobody Complex
| العنوان: | Neutralization of Human Interleukin 23 by Multivalent Nanobodies Explained by the Structure of Cytokine–Nanobody Complex |
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| المؤلفون: | Christian Cambillau, Maarten Van Roy, Aline Desmyter, Hans De Haard, Michael John Scott Saunders, Christophe Blachetot, Carlo Boutton, Geertrui Denecker, Silvia Spinelli, Heidi Rommelaere |
| المساهمون: | Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Department of Biochemistry, Ghent University [Belgium] (UGENT), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), Universiteit Gent = Ghent University [Belgium] (UGENT), Universiteit Gent = Ghent University (UGENT), Architecture et fonction des macromolécules biologiques ( AFMB ), Centre National de la Recherche Scientifique ( CNRS ) -Aix Marseille Université ( AMU ) -Institut National de la Recherche Agronomique ( INRA ), Ghent University [Belgium] ( UGENT ) |
| المصدر: | Frontiers in Immunology Frontiers in Immunology, Frontiers, 2017, 8, pp.884. ⟨10.3389/fimmu.2017.00884⟩ Frontiers in Immunology, Vol 8 (2017) Frontiers in Immunology, 2017, 8, pp.884. ⟨10.3389/fimmu.2017.00884⟩ Frontiers in Immunology, Frontiers, 2017, 8, pp.884. 〈10.3389/fimmu.2017.00884〉 'Frontiers in Immunology ', vol: 8, pages: 884-1-884-10 (2017) |
| بيانات النشر: | HAL CCSD, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Epitope, 0302 clinical medicine, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Interleukin 23, Immunology and Allergy, [ SDV.BIBS ] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Original Research, anti-inflammatory, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, [ SDV.MHEP.ME ] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, Interleukin, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Cell biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030220 oncology & carcinogenesis, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Interleukin 12, lcsh:Immunologic diseases. Allergy, crystal structure, Protein subunit, Immunology, Context (language use), [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 03 medical and health sciences, interleukin 23, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [ SDV.IMM.II ] Life Sciences [q-bio]/Immunology/Innate immunity, Heavy-chain antibody, Rational design, [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, multivalent binder, nanobody, 030104 developmental biology, biology.protein, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, lcsh:RC581-607, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM] |
| الوصف: | International audience; The heterodimeric cytokine interleukin (IL) 23 comprises the IL12-shared p40 subunit and an IL23-specific subunit, p19. Together with IL12 and IL27, IL23 sits at the apex of the regulatory mechanisms shaping adaptive immune responses. IL23, together with IL17, plays an important role in the development of chronic inflammation and autoimmune inflammatory diseases. In this context, we generated monovalent antihuman IL23 variable heavy chain domain of llama heavy chain antibody (VHH) domains (Nanobodies®) with low nanomolar affinity for human interleukin (hIL) 23. The crystal structure of a quaternary complex assembling hIL23 and several nanobodies against p19 and p40 subunits allowed identification of distinct epitopes and enabled rational design of a multivalent IL23-specific blocking nanobody. Taking advantage of the ease of nanobody formatting, multivalent IL23 nanobodies were assembled with properly designed linkers flanking an antihuman serum albumin nanobody, with improved hIL23 neutralization capacity in vitro and in vivo, as compared to the monovalent nanobodies. These constructs with long exposure time are excellent candidates for further developments targeting Crohn's disease, rheumatoid arthritis, and psoriasis. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1664-3224 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::71e4810dbe43a51138194837de049c54 https://hal.archives-ouvertes.fr/hal-01802858/file/fimmu-08-00884.pdf |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....71e4810dbe43a51138194837de049c54 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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