MHC restriction questions

Derek Gray derek.gray at nds.ox.ac.uk
Wed Oct 21 15:43:09 EST 1998


There is also an alternative explanation of why the TCR must not be
allowed to undergo mutation.  Try the following Web site:

http://www.jr2.ox.ac.uk/nds/mbs/Indexa.htm

Derek Gray




Donald Forsdyke wrote:
> 
> Klaus D. Elgert wrote:
> 
> > "Somatic mutation does not occur in the TCR because it would be
> > detrimental to generate self-specific T-cells.  Yet, we display
> > self-peptides in our MHC molecules.  Why haven't we developed
> > mechanisms to display only foreign peptides? Also, if somatic mutation
> > can potentially lead to self-specific T-cells, shouldn't the same hold
> > with B-cells?"
> 
>     A mechanism for intracellular self/not-self discrimination  will be
> found in J. Biol. Systems (1995) vol 3, 273-287 "Entropy-driven protein
> self-aggregation as the basis for self/not-self discrimination in the
> crowded cytosol" (See also J. Theor. Biol. (1994) vol 167, 1-12).
> 
> > I gave the canned answers that random mutation
> > of the TCR may change thymic-induced specificity leading to
> > autoreactivity; there are autoreactive B cells but T cells would
> > control them, polyclonal B-cell activation, etc.
> 
> A generic model ( affinity (specificity) maturation of T and B cells)
> for positive and negative selection may be found in J. Theor. Biol.
> (1975) vol 52, 187-198.
> 
> >  Also, "why not display ONLY foreign peptides?"
> 
> That is what the J. Biol.Sys. paper addresses. For a brief update see
> Cell Stress and Chaperones (1998) vol. 3, suppliment 1, page 3.
> 
> Sincerely,
> Donald Forsdyke (Discussion Leader. Bionet.immunology)



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