prions and immune response

[JARDINE P]

>
Originally I asked:

>>
>> >Technically, if the prion is really a rogue cellular peptide, it
>> >would not ellicit an immune response since it would be auto-immune.
>>
>> >However, if the PrP (Sc) has a different conformation from the PrP
>> >(C) as is speculated, would this provide sufficient epitomes of
>> >"foreign" appearance for the humoral system to kick in.
>
>
Then someone wrote:

>1)  The primary immune response is a low affinity response and so not
>sufficiently fine tuned enough to differentiate between PrPc and PrPsc.
>All primary clones, therefore, that recognise PrPsc will consequently be
>able to recognise PrPc and so have already been ablated or suppressed.
>
>Dr. Martin Cann of the Prion Posse (with a little help from MR. Lionel
>Wightman).
>
Which brings up something I was wondering.
If "all" the clones responding to the PrP are the same, where is the
structural difference between PrP (c) and PrP (sc). One of the
models for prion transmissibility is based on the conformational
change in PrP (sc) being able to allow it to "transform" PrP (c)
into the same altered and diseased state.
The simple answer is that although this structural transformation or
perhaps more appropriately mis-formation is not detectable by the
immune system; i.e. no epitopes of significance exist.
This is not particularly exotic since immunity at this level is hit
and miss. Cross reaction and failure to recognize plague anyone who
has ever done a Western.
Less likely, but far more interesting, is that even though PrP (sc)
is presumably different, it still is recognized as "self".
This is were my thoughts get a little fictional. Could the structure
of PrP (sc) be in fact un-antigenic in the host because the altered
portion is in fact similar to another host peptide, and if so, could
the original appearance of the disease state be catalysed by the
aberant association of this self-peptide with PrP(c).
Or could in fact the whole self-propagating PrP(sc) model be a
little off and there is no mis-formation of PrP(c) catalysed by
PrP(sc).
Yes, Questions.
My brain is starting to hurt.
PJ Jardine