A common antigenic motif recognized by naturally occurring human VH5–51/VL4–1 anti-tau antibodies with distinct functionalities
| العنوان: | A common antigenic motif recognized by naturally occurring human VH5–51/VL4–1 anti-tau antibodies with distinct functionalities |
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| المؤلفون: | Jeroen van Ameijde, Trevin Holland, Hanna Inganäs, Ian A. Wilson, Gabriel Pascual, Hanneke Verveen, Roosmarijn Janson, Donata de Marco, Jeroen J.M. Hoozemans, Esther J. M. Stoop, Stefan Steinbacher, Renske Taggenbrock, Berdien Siregar, Rosa Crespo, Jay Wadia, Wouter Koudstaal, Margot van Winsen, Koen Dockx, Adrian Constantin Apetri, Jaap Goudsmit, Wenli Yu, David Zuijdgeest, Marianne Borgers, Jarek Juraszek, Heng Zhang, Elissa Keogh, Kristof Van Kolen, Kimberley Ummenthum, Martin H. Koldijk, Marc Mercken, Xueyong Zhu, Els C. M. Brinkman-Van der Linden, Michael Mrosek |
| المساهمون: | VU University medical center, Pathology, Amsterdam Neuroscience - Neurodegeneration |
| المصدر: | Acta Neuropathologica Communications, Vol 6, Iss 1, Pp 1-17 (2018) Apetri, A, Crespo, R, Juraszek, J, Pascual, G, Janson, R, Zhu, X, Zhang, H, Keogh, E, Holland, T, Wadia, J, Verveen, H, Siregar, B, Mrosek, M, Taggenbrock, R, Ameijde, J, Inganäs, H, van Winsen, M, Koldijk, M H, Zuijdgeest, D, Borgers, M, Dockx, K, Stoop, E J M, Yu, W, Brinkman-van der Linden, E C, Ummenthum, K, van Kolen, K, Mercken, M, Steinbacher, S, de Marco, D, Hoozemans, J J, Wilson, I A, Koudstaal, W & Goudsmit, J 2018, ' A common antigenic motif recognized by naturally occurring human V H 5-51/V L 4-1 anti-tau antibodies with distinct functionalities ', Acta Neuropathologica Communinications, vol. 6, no. 1, 43, pp. 43 . https://doi.org/10.1186/s40478-018-0543-zTest, https://doi.org/10.1186/s40478-018-0543-zTest Acta Neuropathologica Communinications, 6(1):43. BioMed Central |
| بيانات النشر: | BMC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Monoclonal antibody, medicine.drug_class, Tau protein, Antigenic motif, Epitope, lcsh:RC346-429, Pathology and Forensic Medicine, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Immune system, Antigen, medicine, lcsh:Neurology. Diseases of the nervous system, Microglia, biology, Chemistry, 3. Good health, Cell biology, 030104 developmental biology, medicine.anatomical_structure, biology.protein, Paired helical filaments, Neurology (clinical), Antibody, Alzheimer’s disease, 030217 neurology & neurosurgery |
| الوصف: | Misfolding and aggregation of tau protein are closely associated with the onset and progression of Alzheimer's Disease (AD). By interrogating IgG + memory B cells from asymptomatic donors with tau peptides, we have identified two somatically mutated V H 5-51/V L 4-1 antibodies. One of these, CBTAU-27.1, binds to the aggregation motif in the R3 repeat domain and blocks the aggregation of tau into paired helical filaments (PHFs) by sequestering monomeric tau. The other, CBTAU-28.1, binds to the N-terminal insert region and inhibits the spreading of tau seeds and mediates the uptake of tau aggregates into microglia by binding PHFs. Crystal structures revealed that the combination of V H 5-51 and V L 4-1 recognizes a common Pro-X n -Lys motif driven by germline-encoded hotspot interactions while the specificity and thereby functionality of the antibodies are defined by the CDR3 regions. Affinity improvement led to improvement in functionality, identifying their epitopes as new targets for therapy and prevention of AD. |
| اللغة: | English |
| تدمد: | 2051-5960 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c0cc3ef318c798400926689fc83aaa11Test http://link.springer.com/article/10.1186/s40478-018-0543-zTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c0cc3ef318c798400926689fc83aaa11 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20515960 |
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