I understand that it’s the same sequence but the immune system doesn’t “know” about the sequence, it “knows” about the shape, no? Seems like a misfolded protein would have a different shape and receptors would bind to it differently.

You’re right, antibodies are able to recognize shape. Several early steps of the immune response, however, are independent of conformation. For example, in order to be presented, protein antigens are usually processed and chopped into small peptides, and these may be similar between both prion variants. Additionally, prion proteins can be resistant to that sort of processing.

For more info about what this commenter is talking about:

- https://en.wikipedia.org/wiki/Antigen-presenting_cell

- https://en.wikipedia.org/wiki/Major_histocompatibility_compl...