Novel PrPCWD properties following Wisc-1 propagation in deer expressing PrPC polymorphisms. PrPCWD profiles were obtained from whole hemi-encephalon homogenates derived from orally-infected white-tailed deer expressing different PrPC primary structures (PRNP alleles). A, PK-resistant (res) PrPCWD signatures detected with monoclonal antibodies (mAbs) 12B2 (deer; 93–97), 8G8 (100–105), BAR224 (146–156), and 8H4 (179–189). Expression of histidine or serine at residues 95 and 96, respectively, disrupted 12B2 detection of these PrPCWD allelotypes. For other mAbs, detection of His-95/Ser-96 PK-res PrPCWD required three times more brain protein equivalents. UI, uninfected control. Previously described detection with 8G8 mAb (15) was included for the purpose of comparison. B, linear representation and partial primary sequence of deer PrPC displaying amino acid polymorphisms (red), secondary structural motifs (white boxes: β, β-sheets; α, α-helices), and the epitopes of mAb used for detection; Sha31(148–155). Residues 184 and 200 indicate variable N-linked glycosylation residues; GLP, glycolipid.