The danger of "Danger"

D. R. Forsdyke forsdyke at
Sat Jun 5 10:11:30 EST 1999

Kenneth Frauwirth wrote:

> intracellular self/non-self discrimination.  However, having some
> experience with the antigen processing field, my take on things is that
> the biochemical evidence strongly suggests that non-self peptides are
> *not* preferentially displayed.  Peptides can be extracted from cells and
> analyzed, either by mass spec/sequencing or by T cell recognition, and
> these methods indicate that virally expressed antigens are not presented
> in especially high copy number on MHC Class I; 

  Yes, it is easy to get hung-up on this point. Your logic is that, if
there is intracellular S/NS discrimination (IC-[S/NS]-D)then there
SHOULD be preferential display of NS with MHC. However, this does not
follow. The initial IC-[S/NS]-D acts as an alarm (present even in
unicellular organisms) with multiple secondary effects such as
increasing MHC gene transcription and MHC protein expression (in
multicellular organisms). The actual presentation with MHC of foreign
peptide (derived from NS) is a bonus. 

   In fact, I make a case (in press) that IC-NS can actually recruit
some IC-S, so that the display of the latter may be quantitatively more
important with respect to T-cell attack. (You will recall that T-cell
education is a limited process and there are many T-cells capable of
recognizing complexes of S-peptides with MHC; Schild et al. 1990.
Science 247, 1587-89).  

Sincerely, Donald Forsdyke. Discussion Leader. Bionet.immunology

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