A common antigenic motif recognized by naturally occurring human V_H5-51/V_L4-1 anti-tau antibodies with distinct functionalities.

ABSTRACT: 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_H5-51/V_L4-1 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_H5-51 and V_L4-1 recognizes a common Pro-X_n-Lys mo

SUBMITTER: Apetri A 

PROVIDER: S-EPMC5984341 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature