5V7U

Cyrstal structure of anti-Tau antibody CBTAU-22.1 Fab

Summary for 5V7U

• Entry DOI: 10.2210/pdb5v7u/pdb
• Related: 5V7R
• Descriptor: CBTAU-22.1 Fab light chain, CBTAU-22.1 Fab heavy chain, SULFATE ION, ... (4 entities in total)
• Functional Keywords: antibody, fab, tau protein, alzheimer's disease, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 48173.88

Authors

Zhu, X.,Zhang, H.,Wilson, I.A. (deposition date: 2017-03-20, release date: 2017-04-12, Last modification date: 2024-10-30)

Primary citation

Pascual, G.,Wadia, J.S.,Zhu, X.,Keogh, E.,Kukrer, B.,van Ameijde, J.,Inganas, H.,Siregar, B.,Perdok, G.,Diefenbach, O.,Nahar, T.,Sprengers, I.,Koldijk, M.H.,der Linden, E.C.,Peferoen, L.A.,Zhang, H.,Yu, W.,Li, X.,Wagner, M.,Moreno, V.,Kim, J.,Costa, M.,West, K.,Fulton, Z.,Chammas, L.,Luckashenak, N.,Fletcher, L.,Holland, T.,Arnold, C.,Anthony Williamson, R.,Hoozemans, J.J.,Apetri, A.,Bard, F.,Wilson, I.A.,Koudstaal, W.,Goudsmit, J.
Immunological memory to hyperphosphorylated tau in asymptomatic individuals.
Acta Neuropathol., 133:767-783, 2017

PubMed Abstract: Several reports have described the presence of antibodies against Alzheimer's disease-associated hyperphosphorylated forms of tau in serum of healthy individuals. To characterize the specificities that can be found, we interrogated peripheral IgG memory B cells from asymptomatic blood donors for reactivity to a panel of phosphorylated tau peptides using a single-cell screening assay. Antibody sequences were recovered, cloned, and expressed as full-length IgGs. In total, 52 somatically mutated tau-binding antibodies were identified, corresponding to 35 unique clonal families. Forty-one of these antibodies recognize epitopes in the proline-rich and C-terminal domains, and binding of 26 of these antibodies is strictly phosphorylation dependent. Thirteen antibodies showed inhibitory activity in a P301S lysate seeded in vitro tau aggregation assay. Two such antibodies, CBTAU-7.1 and CBTAU-22.1, which bind to the proline-rich and C-terminal regions of tau, respectively, were characterized in more detail. CBTAU-7.1 recognizes an epitope that is similar to that of murine anti-PHF antibody AT8, but has different phospho requirements. Both CBTAU-7.1 and CBTAU-22.1 detect pathological tau deposits in post-mortem brain tissue. CBTAU-7.1 reveals a similar IHC distribution pattern as AT8, immunostaining (pre)tangles, threads, and neuritic plaques. CBTAU-22.1 shows selective detection of neurofibrillary changes by IHC. Taken together, these results suggest the presence of an ongoing antigen-driven immune response against tau in healthy individuals. The wide range of specificities to tau suggests that the human immune repertoire may contain antibodies that can serve as biomarkers or be exploited for therapy.

PubMed: 28341999
DOI: 10.1007/s00401-017-1705-y

Experimental method

X-RAY DIFFRACTION (1.64 Å)