In article <Pine.3.07.9411070954.A5447-b100000 at alsys1> teitelba at aecom.yu.edu (Rachel Teitelbaum) writes:
>Do you or anyone else know though if the signals that upregulate B7
>expression will be present if self-peptide is in the groove? But then I
>guess that comes back to the question of how the macrophage differentiates
>between self and non-self. Any thoughts?
My thought is that it makes no difference. As I said, the
presenting cell doesn't care whether it is presenting self- or foreign
peptide; all the discrimination is at the level of the T cell.
While there is clearly evidence that B7 upregulation is necessary
to provide co-stimulation, at least in some cases, and that this is
mediated by the MHC II (Nabavi et al, Nature 360:266-8, 1992), this
effect has nothing to do with the peptide in the groove. It is the
interaction with the TcR that causes it, so again it is the T cell that
is responsible. This is supported by the observation that cross-linking
MHC II with antibody also delivers the upregulatory signal; obviously the
antibody isn't discriminating based on the peptide.
Really, the whole point of antigen presentation is that there is
no discrimination based on origin. (There is some filtering based on
structural aspects.) The system is very clean this way - if you have two
sets of cells, why educate both when you can get the same effect by just
educating one?
Ian
--
Ian York (york at mbcrr.harvard.edu)
Dana-Farber Cancer Institute, 44 Binney St., Boston MA 02115
Phone (617)-632-4328 Fax (617)-632-2627