MHC restriction questions

mark mark.haynes at
Thu Oct 22 18:17:01 EST 1998

Ian A. York wrote:
> <snip>
> As to reasons why the system has evolved the way it has, I think the main
> reason is that identification of foreign vs. self (whether peptides or any
> other system) is intrinsically difficult, and therefore costly.  If we're
> still thinking of peptides (note that once we start getting hypothetical
> like this you can postulate other systems of detecting self/non-self, but
> it doesn't change the fundamental problem) it would mean that all peptides
> which could be derived from the 50-100,000-odd self proteins must be
> somehow tagged as 'self", and tagged in a way--this is crucial--that a
> parasite could NEVER evolve similar tags, because that would completely
> overcome the discrimination.

I don't really think you need a system that can differentiate, just a system 
that deletes reactivity to peptides that find there way to the thymus and get 
presented via class i or class ii to cd8 or cd4 thymocytes respectively.  
Everything else is non-self.  You don't need to be tolerant of all the intra 
cellular antigens present from every cell in the body and for the system to 
work (ie to be able to recognize essentially every other protein in the 
universe besides your own) I don't think you would it to. if you tolerize the 
system to to much you might be left with a subset of T cells that recognize 
to little.
> I can't even think of a way in which foreign peptides *could* be RELIABLY
> screened by individual cells, but evolution has a much better imagination
> than I do.  But I do think that there's no way of reducing the cost, and
> that shifting the burden of discrimination from a subset of cells to all
> cells will greatly increase the cost.

Me neither, but I would propose that it would just be shifted to APCs and not 
every cell.

> In other words, it works the way it does because that's the best solution.

and it evolved from a system that was put in place to recognize same as 
opposed to different (yeah it does sound circular, but i do think the 
distinction is important)

> Ian
> --
> Ian York (iayork at <>
> "Bring back the Vicki Robinson .sig virus!" - Cindy Kandolf

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