In article <32m3kjINNso8 at early-bird.think.com>, york at mbcrr.dfci.harvard.edu (Ian
A. York) says:
>In article <94226.084939FORSDYKE at QUCDN.QueensU.CA> <FORSDYKE at QUCDN.QueensU.CA>
>writes:
>> . . . there is the
>>possibility that, over evolutionary time, each gene fine-tunes its protein
>>concentration to the other proteins with which it has been travelling through
>>time.
>>But. (1) If that were the case, surely the evolutionary pressure on
>intracellular parasites would ensure that they too would produce their
>proteins below the aggregation threshold, thus preventing antigen
>presentation altogether.
> Yes, I quite agree. In the papers I elaborate on this and
provide a rationale for the evolution of the heat-shock response
which plays a critical role in ic s/ns discrimination. On the
other hand, at some stage during the life-time of its host a
pathogen may want to leave the host cell (e.g. virus). Thus it
may be forced to exceed the concentration limit regarding its
own proteins.
> (2) This discussion is based on the premise that normal
>intracellular proteins are not presented and therefore an explanation
>is needed as to why they aren't. . As I pointed out this is not
>correct; normal proteins are presented, the process of thymic education
>ensures that T cells do not respond to them.
No, it is not based on that premise. One can postulate a threshold
MHC occupancy rate below which no T cell stimulation would occur.
The following quotation from the J.Biol.Systems paper may help:
"Evidence bearing on the existence and effectiveness of an intracell-
ular s/ns discrimination system might be obtained by comparing the
ratios of peptides derived from self and from not-self proteins which
could be recovered from the purified MHC molecules of cells infected
with viruses (Rammensee et al, 1993). It would be predicted that
virus-derived peptides would be selectively presented. Since s/ns
discrimination would occur at the intracellular (ic) level, negative
selection at the thymus level would be less important. Thus, there
should be many peripheral T cells specific for MHC complexes with
peptides derived from intracellular self proteins, as noted by Schild
and coworkers (1990)."
Sincerely, Don Forsdyke
Discussion Leader. Bionet.immunology
