Characterization of four new monoclonal antibodies against the distal N-terminal region of PrP(c)

Alessandro Didonna; Anja Colja Venturini; Katrina Hartman; Tanja Vranac; Vladka Čurin Šerbec; Giuseppe Legname

doi:10.7717/peerj.811

Characterization of four new monoclonal antibodies against the distal N-terminal region of PrP(c)

PeerJ. 2015 Mar 19:3:e811. doi: 10.7717/peerj.811. eCollection 2015.

Authors

Alessandro Didonna^#¹, Anja Colja Venturini^#², Katrina Hartman², Tanja Vranac², Vladka Čurin Šerbec², Giuseppe Legname^{1

3}

Affiliations

¹ Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy.
² Department for Production of Diagnostic Reagents and Research, Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia.
³ ELETTRA-Sincrotrone Trieste S.C.p.A, Trieste, Italy.

^# Contributed equally.

Abstract

Prion diseases are a group of fatal neurodegenerative disorders that affect humans and animals. They are characterized by the accumulation in the central nervous system of a pathological form of the host-encoded prion protein (PrP(C)). The prion protein is a membrane glycoprotein that consists of two domains: a globular, structured C-terminus and an unstructured N-terminus. The N-terminal part of the protein is involved in different functions in both health and disease. In the present work we discuss the production and biochemical characterization of a panel of four monoclonal antibodies (mAbs) against the distal N-terminus of PrP(C) using a well-established methodology based on the immunization of Prnp (0/0) mice. Additionally, we show their ability to block prion (PrP(Sc)) replication at nanomolar concentrations in a cell culture model of prion infection. These mAbs represent a promising tool for prion diagnostics and for studying the physiological role of the N-terminal domain of PrP(C).

Keywords: Histopathology; Monoclonal antibodies; Prion inhibition; Prion protein.

Grants and funding

This study was supported by the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no 222887—the PRIORITY project to Giuseppe Legname, and by the Slovenian Research Agency with Research Programme P4-0176, Research Project L3-0206 and with a PhD grant to Anja Colja Venturini. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.