NR AWDD
AU Cernilec,M.; Venturini,A.; Koren,S.; Hafner Bratkovic,I.; Curin Serbec,V.
TI Determination of an epitope on the recombinant bovine PrP that provokes the immune response in wild type mice
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions S-04
PT Konferenz-Poster
AB High degree of conservation of the prion protein (PrP) amino acid sequence across mammalian species is supposed to be the reason for the absence of the immune response in prion diseases. However, monoclonal antibody (mAb) E12/2 was obtained from wild-type mouse, that developed prominent humoral immune response against chemically unaltered recombinant bovine PrP (recBoPrP). This mAb specifically recognizes bovine and human PrP, but not PrP from several other mammals and also reacts with truncated forms of PrP (recHuPrP 90-230 and recHuPrP 123-230). From the primary structure comparison of PrPs from all tested species we anticipated that residue 155 (according to human PrP sequence numbering) might be crucial for binding. That was proven by site-directed mutagenesis, since the substitution of His155 to Tyr abolished the reactivity to mutated recHuPrP 23-230. Structural comparison of human, bovine, mouse PrP and H155Y recHuPrP showed that the failure of mAb E12/2 to recognize mouse PrP and H155Y recHuPrP can be explained by this amino acid substitution, as in addition to known differences between these two amino acids the orientation of Tyr compared to His is significantly different. This structural difference strongly suggests increased immunogenicity of this part of recBoPrP. Besides, C-terminal end of helix-1 has already been reported to be important for the species barrier between hamster and mouse that also differ in residue 155.
AD M. Cernilec, A. Venturini, S. Koren, V. Curin Serbec: Blood Transfusion Centre of Slovenia, Slajmerjeva 6, 1000 Ljubljana, Slovenia; I. Hafner-Bratkovic: National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia. 1 E-mail: maja.cernilec@ztm.si
SP englisch
PO Italien