Epitope mapping of 2E2-D3, a monoclonal antibody directed against human TDP-43

TDP-43 is now known to be a major component of ubiquitin-positive, tau-negative inclusions in frontotemporal lobar degeneration with ubiquitin-positive inclusions and sporadic amyotrophic lateral sclerosis. In this study, we mapped the epitope for the monoclonal anti-TDP-43 antibody 2E2-D3. Our mapping and peptide competition experiments showed that the antibody reacted with human TDP-43, but not mouse or rat TDP-43, and recognized amino acids 205–222 of human TDP-43, corresponding to a part of the second RNA recognition motif. These findings suggest that 2E2-D3 is a useful antibody for the characterization of mouse lines transgenic for human TDP-43.