Self/nonself discrimination

FORSDYKE at QUCDN.QueensU.CA FORSDYKE at QUCDN.QueensU.CA
Wed Aug 10 08:26:43 EST 1994


In article <325mua$1me at lyra.csx.cam.ac.uk>, mrc7 at cus.cam.ac.uk (Dr M.R. Clark)
says:
>In article <94211.144113FORSDYKE at QUCDN.QueensU.CA>,
> <FORSDYKE at QUCDN.QueensU.CA> wrote:
>>In article <31bhe8$3f1 at agate.berkeley.edu>, frauwirt at mendel.Berkeley.EDU (Ken
>>Frauwirth (BioKen)) says:
>>
>>>How could a cell recognize a "non-self" antigen (e.g. viral protein) that
>>>was synthesized by its own ribosomes?
>>
>>     It is proposed that over evolutionary time cells have fine-tuned self
>>protein concentrations to the concentrations of the other self proteins with
>>which they are moving through time. The cytosol is so crowded that each
>
>I cannot accept this argument about concentration because it assumes that
>there
>is no genetically or enviromentally determined differences between diverse
>individuals which can still lead to tolerance.
>Any reasonable hypothesis for tolerance must allow the system to operate      t
>without
>prior knowledge of what self is genetically! Most of us are after all outbred!

   Yes, we are outbred, but we only breed within (and thus define) our own
species. We are not threatened intracellularly by other members of our own
species. Within the species framework, cytosolic proteins fluctuate in
concentrations within limits determined by evolutionary selection. A mutant
which exceeded those limits would mark itself as 'foreign' and self-destruct
during embryogenesis. A foreign species (virus) which attempted to acquire an
intracellular foothold would have to avoid exceeding the concentration limit
on the proteins it encodes. Above this limit self-aggregation would occur and
the intracellular s/ns discrimination system would be triggered. This would
destroy both the virus and its host cell. For more see J.Th.Biol 167,7-12;
J. Biol.Sys 2, in press.
                            Sincerely,  Don Forsdyke
                                        Discussion Leader. Bionet.immunology



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