Regarding the infectivity of naked DNA

[Olav Hungnes]

Pearse Ward (wardp at herald.usask.ca) wrote:
: In article <3pqrkp$qql at cisunix1.dfci.harvard.edu>,
: york at mbcrr.dfci.harvard.edu (Ian A. York) wrote:

: > In article <wardp-2205951312040001 at oisin.usask.ca> wardp at herald.usask.ca
: (Pearse Ward) writes:
: > >
: > >What's the evidence that said mice were protected by muscle cells
: > >expressing viral proteins, as opposed to say APC's taking up the DNA? I
: > 
: > Some of the papers explicitly show that the muscle cells express the gene 
: > of interest.  It seems almost impossible that some APC is not also 
: > transfected at very low frequency and that they are responsible for the 
: > protection; but the simpler explanation is preferred.
: > 
: I've read the papers and seen some evidence from people working here that
: muscle cells can take up naked DNA, and that they can express foreign
: cell-surface proteins, but so far i haven't seen any data that show
: conclusively that this is the source of the immune response. Although this
: may be the preferred explaination, it doesn't meant that it is the right
: explaination.

: The implication from this work is that the immune response generated is
: cell-mediated immunity. Without antigen recognition by CD4+ cells, I don't
: see how this is possible. Therefore, for this system to be working as
: advertised, there must be some explaination as to how the exogenous
: antigen gets presented to Th cells.

: Pearse

You don't have to postulate that MHC class II+ cells presenting
antigen to T helper cells are themselves transfected with the 
injected DNA, as peptides presented on MHC class II molecules
may very well be of exogenous origin (e.g. secreted or leaked
from muscle cells).

In the epidermal gene gun-system I feel that the APCs (read:
Langerhans cells) must be more directly involved.

Olav
--
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Olav Hungnes                 olav.hungnes at embnet.uio.no
National Institute               Phone  (+47)22042200
of Public Health                 FAX    (+47)22353605
Oslo, NORWAY
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