Statistical significance was determined by two-tailed Student's t test. A value of p,0.05 was considered statistically significant. Figure S1 CD4 + T cell recruitment into the spinal cord during acute EAE. CD4 + T cells were visualized in 10 mm frozen sections of spinal cords from wt and GFAPcR1D tg mice at day 18 p.i. Immunoperoxidase stain (NovaRED chromogen with hematoxylin counterstain). Scale bars = 50 microns. (TIF)  Influence of Mabs on PrP(Sc) Formation Using In Vitro and Cell-Free Systems PrP(Sc) is believed to serve as a template for the conversion of PrP(C) to the abnormal isoform. This process requires contact between the two proteins and implies that there may be critical contact sites that are important for conversion. We hypothesized that antibodies binding to either PrP(c)or PrP(Sc) would hinder or prevent the formation of the PrP(C)–PrP(Sc) complex and thus slow down or prevent the conversion process. Two systems were used to analyze the effect of different antibodies on PrP(Sc) formation: (i) neuroblastoma cells persistently infected with the 22L mouse-adapted scrapie stain, and (ii) protein misfolding cyclic amplification (PMCA), which uses PrP(Sc) as a template or seed, and a series of incubations and sonications, to convert PrP(C) to PrP(Sc). The two systems yielded similar results, in most cases, and demonstrate that PrP-specific monoclonal antibodies (Mabs) vary in their ability to inhibit the PrP(C)–PrP(Sc) conversion process. Based on the numerous and varied Mabs analyzed, the inhibitory effect does not appear to be epitope specific, related to PrP(C) conformation, or to cell membrane localization, but is influenced by the targeted PrP region (amino vs carboxy). Prion diseases are a group of fatal neurodegenerative disorders that are associated with conformational conversion of the cellular prion protein, PrP C , which is mainly a-helical with very few beta sheets, into a b-sheet-rich form, PrP Sc [1] [2] [3] [4] [5] . The mechanism by which PrP C is converted to the abnormal isoform is still not clear, but it is presumed to involve a PrP C -PrP Sc complex, with the latter serving as a conformational template [6] . In this model, PrP Sc serves as a template that binds to PrP C and produces a conformational conversion into the abnormal isoform. This raises the issue of whether there are critical contact sites that mediate conversion. If this is the case, interfering with or blocking complex formation should prevent the PrP C to PrP Sc conversion process. Previous reports have described anti-PrP antibodies that can stop or hinder the conversion process add reference 44 and renumber [7] [8] [9] [10] [11] [12] [13] [14] .