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In a recently published article, Paramithiotis et al. describe antibodies specific for the prion Tyr-Tyr-Arg (YYR) repeat motif. These antibodies interact with the pathological isoform of the prion protein (PrPSC), but not with the normal cellular isoform (PrpC). Because of this restricted specificity, they suggest that YYR-specific antibodies could be useful for the diagnosis and treatment of prion diseases (Fig. O. The monoclonal antibodies, all of the IgM isotype, were produced by immunizing mice with a synthetic peptide (CYYRRYYRYY). When coupled to magnetic beads, these YYR-specific antibodies immunoprecipitate Prpsc much more efficiently than PrpC. Notably, the Paramithiotis study did not rely on antibodies to YYR for specific detection of PrP. Their immunoblots were not ultimately probed with Prpsc-specific antibodies, but rather with 'regular' antibodies. The latter can detect PrP (but do not distinguish between Prpsc and PrpC) in a precipitate that could include any protein containing solvent-accessible tyrosine and arginine residues. This report is notably similar to that of Korth et al. 2, who described a Prpsc-specific IgM (designated 15B3) after immunizing with full-length recombinant bovine PrP. The 15B3 epitope consists of three separate, linear segments of PrP (15B3-1, 15B3-2 and 15B3-3). The YYR epitope (bold) identified by Paramithiotis et al. is included in or located near two of the 15B3 segments (underlined): GSDYEDRYYR (l5B3-1) and YYRPVDOYS (l5B3-2). Thus, these two independent studies relying on the same method of immunoprecipitation have identified similar IgM antibodies interacting with the same region on PrP, and possibly with the same YYR motifs.